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Here is a chemical reaction formula: Reactants are:aryl halide:CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=C(C=C(C=C3)F)F)C(=O)OCC)Br;amine:CC(C)N1CCNCC1, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=C(C=C(C=C3)F)F)C(=O)OCC)N4CCN(CC4)C(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a solution of ethyl 6-bromo-4-(2,4-difluorophenylamino)-7-ethoxyquinoline-3-carboxylate (400 mg, 0.89 mmol) and 1-(Isopropyl)piperazine (254 µl, 1.77 mmol) in dioxane was added cesium carbonate (722 mg, 2.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (40.6 mg, 0.04 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (55.2 mg, 0.09 mmol). Reaction vessel in oil bath set to 110 °C. 11am After 5 hours, MS shows product (major peak 499), and SM (minor peak 453). o/n, MS shows product peak. Reaction cooled, concentrated onto silica, and purified on ISCO. 40g column, 1:1 EA:Hex, then 100% EA. 289mg yellow solid. NMR (EN00180-62-1) supports product, but some oxidised BINAP impurity (LCMS 655).

Here is a chemical reaction formula: Reactants are:amine:CN1C=NC2=C1C=C(C(=C2F)N)C(=O)OC;aryl halide:C1=CC=C(C=C1)I, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CN1C=NC2=C1C=C(C(=C2F)NC3=CC=CC=C3)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (441 mg, 0.76 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (279 mg, 0.30 mmol) were added to a round bottom flask which was evacuated and flushed with nitrogen 3 times, anisole (16.600 ml) was added and the mixture evacuated and flushed with nitrogen 3 times and then heated to 50ºC for 10 minutes. Cesium carbonate (6204 mg, 19.04 mmol), methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate (1700 mg, 7.62 mmol) and Iodobenzene (1.023 ml, 9.14 mmol) were stirred in anisole (33.2 ml), the flask was evacuated and flushed with nitrogen three times and then heated to 50ºC. The catalyst mixture was transferred into the flask with the reactants (by syringe) and the mixture heated to 100 °C for 18 hours. The reaction mixture was diluted with isohexane (60 ml) and the solid collected by filtration and washed with more isohexane (30 ml). The solid was slurried in DCM / MeOH and adsorbed onto silica then purified by flash silica chromatography eluting with 2% 3.7N NH3 / MeOH in DCM to give methyl 4-fluoro-1-methyl-5-(phenylamino)-1H-benzo[d]imidazole-6-carboxylate (1310 mg, 57.5 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:CN1C=NC2=C1C=C(C(=C2F)N)C(=O)OC;aryl halide:C1=CC=C(C=C1)I, Reagents are:Solvent:COC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CN1C=NC2=C1C=C(C(=C2F)NC3=CC=CC=C3)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (389 mg, 0.67 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (246 mg, 0.27 mmol) were added to a round bottom flask which was evacuated and flushed with nitrogen 3 times, anisole (14.900 ml) was added and the mixture evacuated and flushed with nitrogen 3 times and then heated to 50ºC for 10 minutes. Cesium carbonate (5474 mg, 16.80 mmol), methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate (1500 mg, 6.72 mmol) and Iodobenzene (0.902 ml, 8.06 mmol) were stirred in anisole (29.8 ml), the flask was evacuated and flushed with nitrogen three times and then heated to 50ºC. The catalyst mixture was transferred into the flask with the reactants (by syringe) and the mixture heated to 100 °C for 18 hours. The reaction mixture was diluted with isohexane (50 ml) the solid collected by filtration and washed with more isohexane (25 ml). The solid was slurried in dichloromethane (40 ml) and methanol (10 ml) and filtered, washing the remaining solid with more dichloromethane / methanol. The filtratre (containing product) was evaporated onto silica and purified by flash silica chromatography, eluting with 2% 3.7N NH3 / MeOH in DCM. Pure fractions were evaporated to dryness to afford methyl 4-fluoro-1-methyl-5-(phenylamino)-1H-benzo[d]imidazole-6-carboxylate (1316 mg, 65.4 %) as a light yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)I;amine:CN1C=NC2=C1C=C(C(=C2F)N)C(=O)OC, Reagents are:Solvent:COC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN1C=NC2=C1C=C(C(=C2F)NC3=CC=CC=C3)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (389 mg, 0.67 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (246 mg, 0.27 mmol) were added to a round bottom flask which was evacuated and flushed with nitrogen 3 times, anisole (14.900 ml) was added and the mixture evacuated and flushed with nitrogen 3 times and then heated to 50ºC for 10 minutes. Cesium carbonate (5474 mg, 16.80 mmol), methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate (1500 mg, 6.72 mmol) and Iodobenzene (0.902 ml, 8.06 mmol) were stirred in anisole (29.800 ml), the flask was evacuated and flushed with nitrogen three times and then heated to 50ºC. The catalyst mixture was transferred into the flask with the reactants (by syringe) and the mixture heated to 100 °C for 18 hours. The reaction mixture was diluted with isohexane (50 m) and the solid collected by filtration and washed with more isohexane (25 ml). The solid was slurried in DCM / MeOH and adsorbed onto silica then purified by flash silica chromatography eluting with 2% 3.7N NH3 / MeOH in DCM to give methyl 4-fluoro-1-methyl-5-(phenylamino)-1H-benzo[d]imidazole-6-carboxylate (1510 mg, 75 %) as a light yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C;amine:C1=CC(=CC=C1N)S(=O)(=O)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC(=O)N(C)C, and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (6.47 g, 27.57 mmol), Sulfanilamide (6.17 g, 35.84 mmol), CESIUM CARBONATE (13.47 g, 41.35 mmol) and XANTPHOS (1.595 g, 2.76 mmol) were stirred in DMA (130 ml). Purged this stirred mixture by bubbling nitrogen through for an hour, then added the Palladium acetate. Heated to 130ºC in a metal block (block at 150ºC) and held at this temperature for 3 hours. LCMS (monitorbase) then showed DP as MH+ = 370.99 and MH- = 369.03 at 1.82 minutes, 84%. Allowed to cool to room temperature. The reaction mixture was evaporated to dryness at 50ºC giving __ a dirty-yellow solid residue. Treated with 150 ml water and the resulting yellow solid filtered off and washed with water. Dried by desiccation under high vacuum over phosphorous pentoxide at room temperature to constant weight. This afforded 11.98 g pale- yellow solid [A]. LCMS(monitorbase) showed it to be DP as MH+ = 370.99 and MH- = 369.03 at 1.83 minutes, 90%. _ _ This material was crystallised from acetonitrile; dissolved up in ~1 litre boiling acetonitrile and the cloudy solution filtered hot through a fluted paper. Crystallisation of product from the filtrate was eventually achieved, with difficulty, by rapid cooling in drikold/acetone and seeding/scratching as it warmed up. Cooled in ice/water then the solid was collected by filtration and washed with chilled acetonitrile. Dried by desiccation under high vacuum at room temperature to constant weight. This afforded 6.03 g creamy-white solid [B]. LCMS (monitorbase) then showed DP as MH+ = 370.99 and MH- = 369.03 at 1.49 minutes, 96%. Material B was combined with the same product from P14-A and this total of 7.32 g recrystallised from the minimum of acetonitrile (~550 ml) with hot filtration again to remove trace insoluble matter. Cooled in ice/water and seeded/scratched to induce crystallisation then stood in the fridge overnight. The solid was collected by filtration and washed with chilled acetonitrile. Dried by desiccation under high vacuum initially at room temperature, then at 60°C, to constant weight. This afforded 5.04 g creamy-white solid [C]. LCMS (monitorbase) then showed DP as MH+ = 371.06 and MH- = 369.08 at 1.85 minutes, 99%. Unfortunately nmr showed entrapped acetonitrile at an unacceptable level (~0.5 equiv.). To remove this material C was stirred in ~100 ml ether for an hour, recollected and washed with ether. Dried at 60°C as before to constant weight. This afforded 4.73 g creamy-white solid [D].

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C;amine:C1=CC(=CC=C1N)S(=O)(=O)N, Reagents are:Solvent:CC(=O)N(C)C;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: XANTPHOS (2.466 g, 4.26 mmol) was added to 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (10g, 42.61 mmol), Sulfanilamide (9.54 g, 55.39 mmol) and CESIUM CARBONATE (20.83 g, 63.92 mmol) in DMA (200 ml) at 20ºC. Nitrogen was bubbled through the reaction mixture for 1 hour then PALLADIUM(II) ACETATE (0.670 g, 2.98 mmol) added. The suspension was stirred at 130 °C for 3 hours. The reaction mixture was filtered then evaporated to dryness. The residue was triturated with water (150 mL) and filtered to give crude product as a cream solid - 90% pure. The crude solid was triturated with hot acetonitrile (300 mL) and filtered to afford crude product as a cream solid - 98% by LCMS. This was combined with the product from EN02084-31 and dissolved in boiling acetonitrile (approx 1 L). The solution was concentrated to 500 mL and cooled to ice bath temperature with stirring. A precipitate formed which and the suspension was stirred at room temperature overnight. The solid was filtered to afford 4-(4-(2,6-dimethylpyridin-3-yloxy)pyridin-2-ylamino)benzenesulfonamide (12.00 g, 76 %) as a cream solid.

Here is a chemical reaction formula: Reactants are:amine:C1=CC(=CC=C1N)S(=O)(=O)N;aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC(=O)N(C)C, and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (2 g, 8.52 mmol), Sulfanilamide (1.91 g, 11.09 mmol), CESIUM CARBONATE (4.17 g, 12.80 mmol) and XANTPHOS (490 mg, 0.85 mmol) were stirred in DMA (40 ml). Purged this stirred mixture by bubbling nitrogen through for an hour, then added the Palladium acetate. Heated to 130ºC in a metal block (block at 150ºC) and held at this temperature for 3 hours. LCMS (monitorbase) then showed DP as MH+ = 370.99 and MH- = 369.03 at 1.83 minutes, 83%. Allowed to cool to room temperature. The reaction mixture was evaporated to dryness at 50ºC giving a light-green solid residue. Attempted to partition this residue between DCM (~50 ml) and saturated aqueous sodium hydrogen carbonate (~50 ml). The insoluble matter was filtered off and washed through with water, then DCM. This dirty-yellow solid was dried by desiccation overnight. Wt = 2.04 g. LCMS showed it to be DP, 94%. This material was crystallised from acetonitrile; dissolved up in ~150 ml boiling acetonitrile and the cloudy solution treated with a little Norit SX4 decolourising carbon. Filtered hot through a fluted paper. Slow crystallisation of a creamy-white solid occurred on cooling to room temperature. Cooled in ice/water then the bulky solid was collected by filtration and washed with chilled acetonitrile. Dried by desiccation under high vacuum at room temperature overnight. This afforded 1.29 g creamy-white bulky solid [A]. LCMS (monitorbase) then showed DP as MH+ = 370.99 and MH- = 369.03 at 1.83 minutes, 99%.

Here is a chemical reaction formula: Reactants are:amine:C1=CC(=CC=C1N)S(=O)(=O)N;aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC(=O)N(C)C;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: XANTPHOS (1.603 g, 2.77 mmol) was added to 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (6.5 g, 27.70 mmol), Sulfanilamide (6.20 g, 36.01 mmol) and CESIUM CARBONATE (13.54 g, 41.55 mmol) in DMA (130 ml) at 20ºC. Nitrogen was bubbled through the reaction mixture for 1 hour then PALLADIUM(II) ACETATE (0.435 g, 1.94 mmol) added. The suspension was stirred at 130 °C for 3 hours. The reaction mixture was cooled to ambient temperature and filtered then evaporated to dryness. The residue was triturated with water (150 mL) and filtered to give crude product as a cream solid which was 90% pure by LCMS. The crude solid was triturated with hot MeCN (300 mL) to give a solid which was collected by filtration and dried under vacuum to give a cream solid (7.86g) which was 95% pure by LCMS. The solid was dissolved in the minimum amount of boiling MeCN (650 mL) and filtered to remove remaining trace solids. The filtrate was concentrated to approximately 400 mL and stirred at ice bath temperature until a precipitate formed. The suspension was stirred at room temperature overnight then filtered to afford a cream solid (6.4g) which was 100% pure by LCMS. Combined with EN02084-42 to get a single larger batch.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)Br;amine:CC(=O)N1CCNCC1, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(=O)N1CCN(CC1)C2=CC(=CN=C2)Br, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3,5-dibromopyridine (1.233 g, 5.20 mmol), 1-(piperazin-1-yl)ethanone (0.734 g, 5.73 mmol), PdOAc2 (0.117 g, 0.52 mmol), XANTPHOS (0.361 g, 0.62 mmol), Cs2CO3 (5.09 g, 15.61 mmol), 1,4-dioxane as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with the peak at Rf1.24 showed a fragment mass of 284. Evaporated solvent. Residue purified by ISCO (0-20% MeOH in EtOAc )to get the desired product 1-(4-(5-bromopyridin-3-yl)piperazin-1-yl)ethanone (0.470 g, 31.8 %). Trial # 1: 3,5-dibromopyridine (407 mg, 1.72 mmol), 1-(piperazin-1-yl)ethanone (231 mg, 1.81 mmol), PdOAc2 (38.6 mg, 0.17 mmol), XANTPHOS (119 mg, 0.21 mmol), Cs2CO3 (1681 mg, 5.16 mmol), 1,4-dioxane as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with the peak at Rf1.22 showed a fragment mass of 284. Evaporated solvent. Residue purified by ISCO (0-20% MeOH in EtOAc )to get the desired product 1-(4-(5-bromopyridin-3-yl)piperazin-1-yl)ethanone (118mg, 24%).

Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:C1=CC(=CC=C1N)N2C=CN=C2, Reagents are:Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=CC=C(C=C3)N4C=CN=C4)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: [Reactants], 8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.120 g, 0.44 mmol), Palladium(II) acetate (9.81 mg, 0.04 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.015 g, 0.04 mmol) and Cesium carbonate (0.427 g, 1.31 mmol) in DME (2.5 mL) were placed in a microwave vial and flushed with argon. The reaction mixture was then run in the microwave at 100°C for 1 hr. Reaction not complete. Run for another 30 minutes in the microwave. Still not complete. Added 0.1 eq of Palladium(II)acetate and 0.1 eq of 2-(Dicyclohexylphosphino)biphenyl and let the reaction mixture run in the microwave for additional 45 minutes. Reaction complete. The reaction mixture was filtrated through celite and the filtrate was concentrated. The crude product was purified by preparative chromatography giving 0.072 g (41%) of the product. N-(4-(1H-imidazol-1-yl)phenyl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

Here is a chemical reaction formula: Reactants are:aryl halide:CC(=O)N1CC(OC2=C(C1)C=CC(=N2)Cl)C3=CN=CC=C3;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5=CN=CC=C5)C(=O)C)C=C3)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1-(8-chloro-2-(pyridin-3-yl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanone (0.043 g, 0.14 mmol), Palladium(II) acetate (3.18 mg, 0.01 mmol), 2-(Dicyclohexylphosphino)biphenyl (4.96 mg, 0.01 mmol) and Cesium carbonate (0.138 g, 0.42 mmol) were placed in a microwave vial and flushed with argon. DME (2 mL) was added and the reaction mixture was run in the microwave at 100°C for 60 minutes. No product according to LCMS. Added 0.1 eq of Palladium(II) acetate (3.18 mg, 0.01 mmol) and 0.1 eq of 2-(Dicyclohexylphosphino)biphenyl (4.96 mg, 0.01 mmol) and flushed with argon. Run in the microwave at 100°C for 30 minutes and the reaction was complete. The reaction mixture was filtrated through celite and concentrated. The crude product was purified by prep-HPLC. The solvent was evaporated and partitioned between sat. NaHCO3 and dichloromethane. The organic layer was separated, dried (MgSO4) and concentrated giving 0.0234 g (35%) of the product.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3=CN=CC=C3;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, Reagents are:Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5=CN=CC=C5)C)C=C3)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: [Reactants], Palladium(II) acetate (5.29 mg, 0.02 mmol), 2-(Dicyclohexylphosphino)biphenyl (8.26 mg, 0.02 mmol) and Cesium carbonate (0.230 g, 0.71 mmol) were placed in a microwave vial and flushed with argon. DME (2 mL) was added and the reaction mixture was run in the microwave at 100°C for 60 minutes. Reaction not complete. Added 0.1 eq of Palladium(II) acetate (5.29 mg, 0.02 mmol) and 0.1 eq of 2-(Dicyclohexylphosphino)biphenyl (8.26 mg, 0.02 mmol) and flushed with argon. Run in the microwave at 100°C for 60 minutes and the reaction was complete. The reaction mixture was filtrated through celite and concentrated. The crude product was purified by prep-HPLC. The solvent was evaporated and partitioned between sat. NaHCO3 and dichloromethane. The organic layer was separated, dried (MgSO4) and concentrated giving 0.029 g (28%) of the product.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N;aryl halide:C1=CN=C(C=C1F)Cl, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC(C)(C)OC(=O)NC1=NC=CC(=C1)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-chloro-4-fluoropyridine (132 mg, 1 mmol), tert-butyl carbamate (123 mg, 1.05 mmol), CESIUM CARBONATE (652 mg, 2.00 mmol) ,TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (36.6 mg, 0.04 mmol) and 9,9-DIMETHYL-4,5-BIS(DIPHENYLPHOSPHINO)XANTHENE (46.3 mg, 0.08 mmol) were suspended in 1,4-dioxane (2.5 ml) ,degased with argon and heated to 90 °C for 4 hours. After cooling the reaction was quenched with water and extracted with ethyl acetate ( x 2 ). The combined organic phases were washed with water , a saturated aqueous solution of brine , dried over magnesium sulfate , concentrated then purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford tert-butyl 4-fluoropyridin-2-ylcarbamate (41.3 mg, 19.46 %).

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC2=NC=C(N2C=C1)C3=NC(=NC=C3Cl)Cl;amine:COC1=C(C=CC(=C1)C=O)N, Reagents are:Base:C1CCC2=NCCCN2CC1;Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:COC1=C(C=CC(=C1)C=O)NC2=NC=C(C(=N2)C3=CN=C4N3C=CC=C4)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3-(2,5-dichloropyrimidin-4-yl)imidazo[1,2-a]pyridine (4 g, 15.09 mmol), 4-amino-3-methoxybenzaldehyde (2.281 g, 15.09 mmol), 9,9-DIMETHYL-4,5-BIS(DIPHENYLPHOSPHINO)XANTHENE (0.873 g, 1.51 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.345 g, 0.38 mmol) and 1,8-DIAZABICYCLO [5.4.0] UNDEC-7-ENE (5.64 ml, 37.72 mmol) were dissolved in Dioxane (120 ml) then degazed and purged with argon. The reaction was heated to reflux (bath 120°C) for 2H30. Reaction mixture was filtered through a filter cup and concentrated. FR01132-77-01 w=14.65 g The crude product was purified by flash chromatography (NOVASEP) on silica gel ( 15-40µm ) eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 4-(5-chloro-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxybenzaldehyde (34.9 %) as a clear yellow solid. PBO-01132-77-02 w=2 g

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), racemic-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (101 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 81 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+];metal and ligand:CC1=CC=CC=C1P(C2=CC=CC=C2C)C3=CC=CC=C3C;metal and ligand:[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), Tri-o-tolylphosphine (49.4 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 88 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F, Reagents are:Base:CCC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3;metal and ligand:[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), Triphenylphosphine (0.038 mL, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 73 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+];metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (91 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 79 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:[Pd];Base:CCC(C)(C)[O-].[Na+], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (94 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 85 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC(=C(C=C2)Br)F, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:COC1=C(C(=CC=C1)OC)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;metal and ligand:[Pd];Base:CCC(C)(C)[O-].[Na+], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), 2-Dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (66.6 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 85 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:C1OC2=C(O1)C(=C(C=C2)Cl)N;aryl halide:CC(=O)NC1=NC=CC(=C1)Cl, Reagents are:Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(=O)NC1=NC=CC(=C1)NC2=C(C=CC3=C2OCO3)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Reaction carried out in two batches in 20 ml microwave tubes. 5-chlorobenzo[d][1,3]dioxol-4-amine (1 g, 5.83 mmol), N-(4-chloropyridin-2-yl)acetamide (0.994 g, 5.83 mmol), XANTPHOS (0.405 g, 0.70 mmol), PALLADIUM(II) ACETATE (0.065 g, 0.29 mmol) and CESIUM CARBONATE (3.80 g, 11.66 mmol) were suspended in 2x DMA (12mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. LC/MS showed completion. The reaction mixture was concentrated and diluted with EtOAc , and washed sequentially with water and saturated brine. The organic layer was dried over MgSO4, filtered and evaporated. The crude oil was triturated with EtOAc, Et2O and hexane to give a solid which was collected by filtration and dried under vacuum to give P1 N-(4-(5-chlorobenzo[d][1,3]dioxol-4-ylamino)pyridin-2-yl)acetamide (680mg, 38%)as a tan solid. NMR of this product showed product plus some DMA and aromatic impurities. The filtrate from the the above was concentrated and triturated again to give P2 N-(4-(5-chlorobenzo[d][1,3]dioxol-4-ylamino)pyridin-2-yl)acetamide (800mg, 45%) as a pale orange solid. NMR of this product showed it to be much cleaner than P1.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (0.205 g, 0.91 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (5 g, 18.26 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (3.22 g, 18.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.056 g, 1.83 mmol) and cesium carbonate (8.92 g, 27.38 mmol) dissolved in 1,4-dioxane (100 mL). The resulting suspension was degassed (3 times) with nitrogen and was stirred at 100°C for 16 hours. The reaction mixture was allowed to cool to room temperature, diluted with DCM (100 mL) and filtered. The residue was washed with DCM. The filtrates was combined evaporated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (2.500 g, 42.5 %) as a pale yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (24.59 mg, 0.11 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (600 mg, 2.19 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (386 mg, 2.19 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (127 mg, 0.22 mmol) and cesium carbonate (1071 mg, 3.29 mmol) in 1,4-dioxane (10 mL). The resulting suspension was degassed with nitrogen and was stirred at 100 °C for 18 hours. Reaction was allowed to cool to room temperature, quenched with water and extracted with EtOAc. Combined organic phases were washed with water, brine, dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (447 mg, 63.3 %) as a pale yellow crystalline solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (0.152 g, 0.68 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (3.71 g, 13.56 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (2.39 g, 13.56 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.785 g, 1.36 mmol) and cesium carbonate (6.63 g, 20.34 mmol) in 1,4-dioxane (70 mL). The resulting suspension was degassed with nitrogen and was stirred at 100 °C for 18 hours. Reaction was allowed to cool to room temperature, quenched with water (100 mL) and extracted with EtOAc*. Combined organic phases were washed with water, brine, dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography* on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (2.160 g, 49.4 %) as a yellow crystalline solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (0.573 g, 2.55 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (13.99 g, 51.07 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (9 g, 51.07 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.96 g, 5.11 mmol) and cesium carbonate (24.96 g, 76.61 mmol) dissolved in 1,4-dioxane (300 mL). The resulting suspension was degassed (3 times) with nitrogen and was stirred at 100°C for 16 hours. The reaction mixture was allowed to cool to room temperature, diluted with DCM (100 mL) and filtered. The residue was washed with DCM. The filtrates was combined and evaporated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (9.80 g, 59.6 %) as a clear white solid.

Here is a chemical reaction formula: Reactants are:amine:CONC(=O)C1=CC=CC=C1N;aryl halide:C1=C(C(=CN=C1Cl)Cl)I, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,5-dichloro-4-iodopyridine (75 g, 273.84 mmol), 2-amino-N-methoxybenzamide (47.8 g, 287.53 mmol), cesium carbonate (107 g, 328.60 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (11.88 g, 20.54 mmol) were suspended in 1,4-dioxane (913 ml). Nitrogen was bubbled through the mixture for 20 minutes then diacetoxypalladium (3.07 g, 13.69 mmol) was added. Reaction was heated to reflux overnight under nitrogen. Reaction was allowed to cool to ~50°C and filtered. Filtered cake was washed with hot EtOH (2x300 mL) _._ Filtrate was concentrated to dryness to afford crude as a black solid (57 g). Filtered cake was re-washed with CH2Cl2/MeOH 9/1 (3x300 mL). Filtrate was combined with previous crude and concentrated to dryness to afford crude as a black solid (93 g). Crude was stirred in boiling EtOH (380 mL). Insoluble was filtered => _seemed to contain expected product / instantaneous cristallisation occured in the filtrate_. Flask was left standing overnight. Resulting crystals were filtered, washed with Et2O (x2) and dried to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (33.4 g, 39.1%, EN03787-93-02) as a dark grey crystalline solid => _product crystallised with 1eq of EtOH._ Insoluble material was washed with EtOH, CH2Cl2 and dried overnight to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (26.6 g, EN03787-93-01) => _not fully soluble in DMSO, seemed contaminated by minerals._ It was suspended in H2O (200 mL) and stirred at room temperature for 20 minutes. It was filtered, washed with EtOH (x2) and dried to afford an orange solid (3.8 g !!) => _not soluble in DMSO, probably only a few expected product in it !!_

Here is a chemical reaction formula: Reactants are:amine:CONC(=O)C1=CC=CC=C1N;aryl halide:C1=C(C(=CN=C1Cl)Cl)I, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,5-dichloro-4-iodopyridine (10.4 g, 37.97 mmol), 2-amino-N-methoxybenzamide (6.63 g, 39.87 mmol), cesium carbonate (14.85 g, 45.57 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.648 g, 2.85 mmol) were suspended in 1,4-dioxane (130 mL). Nitrogen was bubbled through the mixture for 10 minutes then diacetoxypalladium (0.426 g, 1.90 mmol) was added. Flask was purged with nitrogen 3 times and heated to reflux for 16 hours. Reaction was allowed to cool to room temperature and diluted with CH2Cl2 (100 mL) (=> _trouble_ ) + MeOH (10 mL). Mixture was filtered _(filtrate is clear)_ and washed with CH2Cl2/MeOH 9/1 (2x100 mL) => _filtrate became troubled._ Filtrate was concentrated to dryness to afford crude as a dark brown solid (17.5 g). Filtered cake seemed to contain some product. It was suspended in H2O (200 mL) and stirred for 20 minutes. It was then filtered ( _long and tricky filtration !!_ ). Solid was dissolved in CH2Cl2/MeOH ( _big volume compare to the amount of solid !! it's quite insoluble_ ), dried over MgSO4 and concentrated to dryness to afford crude product (0.5 g...) as a dark green solid. Solids were combined (18 g) and recristallised from EtOH (85 mL). Flask was left standing over the weekend. Resulting crystals were filtered, washed with Et2O and dried to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (8.20 g, 69.2 %) as a dark yellow crystalline solid => _product crystallised with 1eq of EtOH._ Filtrate was concentrated. Residue (7.7 g) was recristallised from EtOH (30 mL). Hot solution was seeded with crystals, from 1st batch, and flask was left standing overnight. Resulting crystals were filtered, washed with Et2O and dried to afford a dark yellow crystalline solid (1.68 g, EN03787-82-02) => _impure material (see UPLCMS & 1H NMR 03787-82-02)_

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CNC(=O)C1=CC=CC=C1N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-amino-N-methylbenzamide (110 mg, 0.73 mmol), 2,5-dichloro-4-iodopyridine (200 mg, 0.73 mmol), diacetoxypalladium (8.20 mg, 0.04 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (42.3 mg, 0.07 mmol) and cesium carbonate (357 mg, 1.10 mmol) suspended in 1,4-dioxane (4 mL) was weighed out in a microwave vial and sealed. argon was let to bubble into the mixture for 5 minutes at rt then the resulting mixture was stirred at 100 °C for 1 hour. The reaction mixture was allowed to cool to room temperature under stirring and diluted with dichloromethane. Insolubles were removed by filtration and the filtrate was concentrated. The residue was triturated in DCM, collected by filtration and dried to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methylbenzamide (150 mg, 69.4 %) as a off- white solid.

Here is a chemical reaction formula: Reactants are:amine:CNC(=O)C1=CC=CC=C1N;aryl halide:C1=C(C(=CN=C1Cl)Cl)I, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (0.098 g, 0.44 mmol) was added to 2,5-dichloro-4-iodopyridine (3 g, 10.95 mmol), 2-amino-N-methylbenzamide (1.645 g, 10.95 mmol), Cesium carbonate (7.14 g, 21.91 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.380 g, 0.66 mmol) in dioxane (150 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18 hours. The reaction mixture was filtered and the filtrate was evaporated to dryness. The crude residue was triturated with DCM to give a solid which was collected by filtration and dried under vacuum to give 2-(2,5-dichloropyridin-4-ylamino)-N-methylbenzamide (1.58 g, 49 %) as a tan solid, LCMS indicated 87% pure. This was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methylbenzamide (1.040 g, 32.1 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC(=C(C=C2)Cl)F, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[K+];Solvent:C1COCCO1, and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To degassed 1,4-dioxane (13.900 ml) in a flame-dried and argonflushed 50 mL roundbottomed flask were added 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (386 mg, 1.39 mmol) and 4-(4-chloro-3-fluorobenzyl)morpholine (320 mg, 1.39 mmol) followed by POTASSIUM TERT-BUTOXIDE (203 mg, 1.81 mmol) whilst stirring. The resulting slurry was flushed with argon followed by addition of TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (128 mg, 0.14 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (200 mg, 0.42 mmol), whereafter the dark violet reaction mixture was again flushed with argon and heated to 102 °C and stirred under argon for 15 h. The completion of the reaction was controlled by HPLC and the crude mixture was cooled to ambient temperatuer and then filtrated through Celite and washed through with dichloromethane. The solution was concentrated in vacuo and dissolved in a minimum amount of DMSO and purified via Preparative HPLC. The pooled fractions were concentrated in vacuo and added HCl. 5-fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (60.0 mg, 9.15 %)

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC(=C(C=C2)Cl)F;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[K+], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=C(C=C(C=C4)CN5CCOCC5)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To degassed 1,4-dioxane (39.2 ml) in a flame-dried and argonflushed 250 mL roundbottomed flask were added 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (1.076 g, 3.88 mmol) and 4-(4-chloro-3-fluorobenzyl)morpholine (0.9 g, 3.92 mmol) followed by POTASSIUM TERT-BUTOXIDE (0.572 g, 5.09 mmol) whilst stirring. The resulting slurry was flushed with argon and stirred for 5-10 minutes followed by addition of TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.359 g, 0.39 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso- propyl-1,1'-biphenyl (0.374 g, 0.78 mmol), whereafter the reaction mixture was flushed with argon again and heated to 102 °C and stirred under argon for 3 h. No further conversion occurred after 2 hours. The completion of the reaction was controlled by HPLC and the crude mixture was cooled to ambient temperatuer and then filtrated through Celite and washed through with dichloromethane. The solution was concentrated in vacuo and dissolved in 14 ml dichloromethane and purified by ISCO and then by prep-HPLC. The pooled fractions were concentrated in vacuo and added HCl to give 5-fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (0.227 g, 11.43 %)

Here is a chemical reaction formula: Reactants are:amine:CC1=CN=C(S1)N;aryl halide:C[C@@H](C1=NC=C(C=N1)F)NC2=NC(=NC(=N2)Cl)N3CCOCC3, Reagents are:Solvent:C1COCCO1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=CN=C(S1)NC2=NC(=NC(=N2)N3CCOCC3)N[C@@H](C)C4=NC=C(C=N4)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: (S)-4-chloro-N-(1-(5-fluoropyrimidin-2-yl)ethyl)-6-morpholino-1,3,5-triazin-2-amine (100 mg, 0.29 mmol), 5-methylthiazol-2-amine (50.4 mg, 0.44 mmol), BINAP (18.33 mg, 0.03 mmol), Pd2(dba)3 (13.48 mg, 0.01 mmol) and Cs2CO3 (240 mg, 0.74 mmol) were combined in a microwave reaction tube and vacuum purged. The tube was then charged with nitrogen and dioxane (0.589 mL) was added. The tube was then evacuated again and placed under a nitrogen balloon for 8 hours. LC/MS confirmed formation of the product (m+1 = 418) at t= 2.07 min. The reaction mixture was concentrated in vacuo leaing a brown solid (472 mg). This material was the redissolved in EtOAc, filtered through Celite, washed with water and dried with Na2SO4. Concentration in vacuo gave a rust solid (272 mg). This material was purified by ISCO (0-10% MeOH/DCM). Concentration of the fractions in vacuo gave an orange oil. This material was then repurifed by ISCO (4-8% MeOH/DCM) and (0-4% MeOH/DCM). Both gradients resulted in impure material, so the recovered orange oil was purified again by ISCO (60-100% EtOAc/Hex). Concentration in vacuo gave a yellow solid (34.8 mg). LC/MS showed this material to still be only 80% pure, so it was purified again by ISCO (55-95% EtOAc/Hex). A yellow solid (25.4 mg) was again collected. Although LC/MS and HPLC showed this material to be only ~80% pure, the NMR confirmed this material to be the desired product, (S)-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methylthiazol-2-yl)-6-morpholino-1,3,5-triazine-2,4-diamine, with 95% purity. 1H NMR (300 MHz, CHLOROFORM- _d_ ) d ppm 11.87 (br. s., 1 H) 9.48 (br. s., 1 H) 8.58 (s, 2 H) 7.01 (s, 1 H) 5.35 (t, 1 H) 3.28 - 4.23 (m, 8 H) 2.38 (s, 3 H) 1.59 (d, 4 H)

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C#N)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2-chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamide (200 mg, 0.70 mmol), Palladium(II) acetate (12.53 mg, 0.06 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (155 mg, 1.40 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (48.4 mg, 0.08 mmol) and Cesium carbonate (273 mg, 0.84 mmol) were suspended in dioxane (5 mL) into a test tube. The reaction was purged for 5 mins with nitrogen and then heated to 90 °C for 24 hours with stirring. The reaction was cooled to cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product .The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(5-cyano-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-N-methylbenzamide (126 mg, 50.0 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C#N)Cl;amine:CN1C(=CC(=N1)OC)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C#N)NC3=CC(=NN3C)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2-chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.35 mmol), Palladium(II) acetate (6.26 mg, 0.03 mmol), [Reactants], 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (24.22 mg, 0.04 mmol) and Cesium carbonate (136 mg, 0.42 mmol) were suspended in dioxane (3 mL) into a test tube. The reaction was purged for 5 mins with nitrogen and then heated to 90 °C for 18 hours with stirring. The reaction was cooled to cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product .The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(5-cyano-2-(3-methoxy-1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methylbenzamide (72.0 mg, 54.7 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3C#N)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (595 mg, 1.90 mmol), Palladium(II) acetate (34.2 mg, 0.15 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (132 mg, 0.23 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (423 mg, 3.80 mmol) and Cesium carbonate (744 mg, 2.28 mmol) were suspended in dioxane (40 mL). The reaction was purged for 5 mins with nitrogen and then heated to 90 °C for 2 hour with stirring. The reaction was cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product .The crude product was purified by preparative basic HPLC. Fractions containing the desired compound were evaporated to dryness to afford 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (54.0 mg, 7.33 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3C#N)Cl, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC;Base:C1=CC=C(C=C1)[O-].[Na+], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1,3-dimethyl-1H-pyrazol-4-amine (35.5 mg, 0.32 mmol), 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (50 mg, 0.16 mmol)sodium phenolate (18.56 mg, 0.16 mmol),(R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T- BUTYLPHOSPHINE (8.74 mg, 0.02 mmol) and diacetoxypalladium (2.87 mg, 0.01 mmol) were suspended in DME (1 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. LCMS indicated 47% product, ~8% dimer, ~8% hydrolysed Starting material , Starting material 25% and an unknown 17% @ 2.66 and unknown 12% @ 0.77. Sample combined with en01521-027 and en01521-034, SCX'd and sent to purification group. The crude product was purified by preparative basic HPLC. Fractions containing the desired compound were evaporated to dryness to afford 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (34.0 mg, 54.9 %) as a brown solid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3C#N)Cl, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1,3-dimethyl-1H-pyrazol-4-amine (355 mg, 3.19 mmol), 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (500 mg, 1.60 mmol), Cesium carbonate (625 mg, 1.92 mmol), Palladium(II) acetate (28.7 mg, 0.13 mmol)and (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (87 mg, 0.16 mmol) were suspended in DME (10 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was handed to the purification group and purified by basic preparative HPLC. Fractions containing the desired compound were evaporated to dryness to afford 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (271 mg, 43.8 %) as a brown solid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3C#N)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (500 mg, 1.60 mmol), 1,3-Dimethyl-1H-pyrazol-4-ylamine (355 mg, 3.20 mmol) and Cesium carbonate (625 mg, 1.92 mmol), Palladium(II) acetate (28.7 mg, 0.13 mmol) and (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t- butylphosphine (90 mg, 0.16 mmol) were suspended in DME (10 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. This was combined with reactions EN01370-84-87 and concentrated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Mixed fractions were combined and re-columned. This prcess was repeated a further 3 times! 'Pure' fractions were combined and evaporated to dryness to afford 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (484 mg, 15.63 %) as a yellow solid (1.08g) - 100% by LCMS and clean by TLC but the NMR is not great. Passed onto the purification group.The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the required product. 200mg trial purification - resulted in 137mg pure - EN01370-88-1 Rest of the material processed to give EN01370-88-2 (347mg and 177mg)

Here is a chemical reaction formula: Reactants are:aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N;amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl, Reagents are:Solvent:CC1=CC=CC=C1;Base:C1CCC2=NCCCN2CC1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.190 mL, 1.27 mmol) was added to a mixture of N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (100 mg, 0.51 mmol), 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (105 mg, 0.61 mmol) and BIS(DIBENZYLIDENEACETONE)PALLADIUM(0) (26.3 mg, 0.05 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (29.4 mg, 0.05 mmol) in toluene (1 mL) in a microwave tube. The reaction was degased, purged with argon and heated to 130 °C over a period of 7 hours in an oil bath. The mixture was diluted with dichloromethane, washed with water (emulsion), with brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane. The solvent was evaporated to dryness to afford N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (55.0 mg, 32.5 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N;amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (4 g, 20.34 mmol), 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (3.51 g, 20.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.412 g, 2.44 mmol), diacetoxypalladium (0.228 g, 1.02 mmol) and cesium carbonate (13.26 g, 40.68 mmol) were suspended in 1,4-dioxane (75 mL) and sealed into 5 microwave tubes. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (250 mL) and washed with water (250 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford and orange gum. The gum was dissolved in a little ether, then isohexane was added to precipitate N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (2.180 g, 32.2 %) as a white solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N;amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (0.8 g, 4.07 mmol), 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (0.702 g, 4.07 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.282 g, 0.49 mmol), diacetoxypalladium (0.046 g, 0.20 mmol) and cesium carbonate (2.65 g, 8.14 mmol) were suspended in 1,4-dioxane (15 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was evaporated and partitioned between EtOAc (50 mL) and water (50 mL). The mixture was filtered and the organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (0.384 g, 28.4 %) as a white solid. Impure fractions were combined and purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford more crude material. This material was triturated with DCM to afford a second batch of the material.

Here is a chemical reaction formula: Reactants are:aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N;amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (1 g, 5.09 mmol), 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (0.878 g, 5.09 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.324 g, 0.56 mmol), diacetoxypalladium (0.090 g, 0.40 mmol), cesium carbonate (4.14 g, 12.71 mmol) and dioxane (18 mL) was degased, purged (x3) with argon and heated to reflux over a period of 4 hours in an oil bath (110°C). The reaction was complete. The reaction mixture was allowed to warm to room temperature diluted with water (25ml), a saturated solution of NH4Cl (35ml). Extraction with dichloromethane (x2), the organic was washed with a saturated aqueous solution of brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 2% methanol in dichloromethane. The solvent was evaporated, the product was diluted in dichloromethane. The solution was filtered through PTFE filter 0.45µm, the filtrate was concentrated to dryness to afford N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (1.200 g, 70.9 %) as a white crystalline solid.

Here is a chemical reaction formula: Reactants are:amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl;aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (0.8 g, 4.07 mmol), 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (0.702 g, 4.07 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.282 g, 0.49 mmol), diacetoxypalladium (0.046 g, 0.20 mmol) and cesium carbonate (2.65 g, 8.14 mmol) were suspended in 1,4-dioxane (15 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (50 mL) and washed with water (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (0.592 g, 43.7 %) as a white solid.

Here is a chemical reaction formula: Reactants are:amine:CCN1CCNCC1;aryl halide:C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=C5C(=C(C=C4)I)C6=CC=CC=C6S5, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CCN1CCN(CC1)C2=C3C4=CC=CC=C4SC3=C(C=C2)C5=CC=CC6=C5OC(=CC6=O)N7CCOCC7, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 8-(1-iododibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (2 g, 3.71 mmol), 2,2'-BIS(DIPHENYLPHOSPHINO)-1,1'-BINAPHTHYL (0.462 g, 0.74 mmol), CESIUM CARBONATE (3.62 g, 11.12 mmol) and PALLADIUM (II) ACETATE (0.166 g, 0.74 mmol) were weighed out in a flask and inerted with argon. toluene (25 ml) and 1-ethylpiperazine (0.942 ml, 7.42 mmol) were added and the mixture was degassed several times with argon. The reaction was stirred at 110 °C (bath) for 2 hours. The reaction was incomplete. 2,2'-BIS(DIPHENYLPHOSPHINO)-1,1'-BINAPHTHYL (0.462 g, 0.74 mmol) and PALLADIUM (II) ACETATE (0.166 g, 0.74 mmol) were added, the reaction mixture was purged with argon, and the mixture was stirred at 110 °C for 5 hours. Reaction was quite clean: Crude LCMS showed very little de-iodo by-product and starting material left. The reaction was diluted with dichloromethane and insolubles were removed by filtration. The filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated, the resulting solid was stirred in diethyl ether (40 ml) for 2 days. The product was filtered to give a solid which was collected by filtration and dried under vacuum to give 8-(1-(4-ethylpiperazin-1-yl)dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (0.950 g, 48.7 %) as a pale beige solid. Melting point: 221-224°C Purity check: 99%, Et2O: 0.06 mole/mole, H2O: 0.3 mole/mole H NMR strength: 97% +/- 3%

Here is a chemical reaction formula: Reactants are:amine:CCN1CCNCC1;aryl halide:C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=C5C(=C(C=C4)I)C6=CC=CC=C6S5, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:CCN1CCN(CC1)C2=C3C4=CC=CC=C4SC3=C(C=C2)C5=CC=CC6=C5OC(=CC6=O)N7CCOCC7, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 8-(1-iododibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (20 mg, 0.04 mmol), 1-ethylpiperazine (9.42 µl, 0.07 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.145 mg, 3.71 µmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.849 mg, 0.93 µmol) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (16.62 µl, 0.11 mmol) were suspended in dioxane (250 µl) and sealed into a microwave tube. The reaction was degased, purged with argon and heated to 130 °C over a period of 45 minutes in the microwave reactor. No reaction.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCNCC1;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 4-bromo-1-methoxy-2-nitrobenzene (30 g, 129.29 mmol), 1-(piperazin-1-yl)ethanone (16.57 g, 129.29 mmol), cesium carbonate (84 g, 258.59 mmol),diacetoxypalladium (2.322 g, 10.34 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.98 g, 15.52 mmol) in dioxane (200 mL) were degazed with nitrogen and stirred at 100°C for 1 hour. The reaction mixture was allowed to cool to room temperature, water (1000mL) was added and mixture was filtered on celite. The aq. layer was extracted with CH2Cl2 (2X500mL). The organic layer was dried on MgSO4, filtered and concentrated to dryness to afford the crude product. This product was purified by flash chromatography on silica gel eluting with ethyl acetate - methanol (92-8), the solvents were evaporated to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (10.80 g, 29.9 %)

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCNCC1;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1-(piperazin-1-yl)ethanone (9.94 g, 77.58 mmol), Cesium carbonate (50.6 g, 155.15 mmol), XANTPHOS (5.39 g, 9.31 mmol) and Pd(OAc)2 (1.393 g, 6.21 mmol) were added to a stirred solution of 4-bromo-1-methoxy-2-nitrobenzene (18 g, 77.58 mmol) dissolved in dioxane (120 ml). The resulting suspension was heated to 120 °C (bath) over a period of 1 hour. The reaction mixture was allowed to cool and the residual cesium carbonate was removed by filtration through a pad of Dicalite speed plus, washing with dichloromethane. The solvent was removed under reduced pressure to give a dark oil. PBO-02628-53-01 w= 45 g The crude product in solution in DCM was added to a silica gel column and was eluted with methanol 0 to 20% in EtOAc (NOVASEP). Collected fractions to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (17.96 g, 83 %) as a yellow solid. PBO-02628-53-02

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCNCC1;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 4-bromo-1-methoxy-2-nitrobenzene (1.5 g, 6.46 mmol), 1-(piperazin-1-yl)ethanone (0.829 g, 6.46 mmol), CESIUM CARBONATE (4.21 g, 12.93 mmol), XANTPHOS (0.449 g, 0.78 mmol) and PdOAc2 (0.116 g, 0.52 mmol) were suspended in dioxane (20 ml) and sealed into a microwave tube. The reaction was heated to 120 °C for 90 minutes in the microwave reactor and cooled to RT. The reaction mixture was filtered through celite with ethyl acetate (50 mL). The filtrate was evaporated to dryness. The crude product was purified by flash silica chromatography in EtOAc. Pure fractions were evaporated to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (0.022 g, 1.218 %) as a brown solid.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCNCC1;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 4-bromo-1-methoxy-2-nitrobenzene (1.5 g, 6.46 mmol) was added in one portion to 1-(piperazin-1-yl)ethanone (0.829 g, 6.46 mmol), CESIUM CARBONATE (4.21 g, 12.93 mmol), XANTPHOS (0.449 g, 0.78 mmol) and PdOAc2 (0.116 g, 0.52 mmol) in dioxane (20 ml) under nitrogen. The resulting mixture was stirred at 120 °C for 3 hours. The reaction mixture was filtered through celite and the fitrate evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (0.025 g, 1.385 %) as a brown oil.

Here is a chemical reaction formula: Reactants are:aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl;amine:CC1=NN(C=C1N)C, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (250 mg, 0.80 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (134 mg, 1.20 mmol), Sodium tert-butoxide (115 mg, 1.20 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (55.6 mg, 0.10 mmol) and BIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (58.7 mg, 0.06 mmol) were suspended in dioxane (15 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. Reaction not complete by LCMS so more 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (55.6 mg, 0.10 mmol), BIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (58.7 mg, 0.06 mmol) and 1,3-dimethyl-1H-pyrazol-4-amine (134 mg, 1.20 mmol) were added and the reaction heated to 150 ºC for a further 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product as a tan gum. The sample was given to the purification group for purification by preparative HPLC. Fractions containing the desired compound were evaporated to dryness to afford 2-(5-chloro-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (44.3 mg, 14.30 %) as a tan solid.

Here is a chemical reaction formula: Reactants are:amine:CC1CNCC(N1)C;aryl halide:COC1=C(C=CC(=C1)Br)NC2=NC=C(C(=N2)C3=CN=C4N3C=CC=C4)Cl, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1CN(CC(N1)C)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC=C5)Cl)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: N-(4-bromo-2-methoxyphenyl)-5-chloro-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine (107 mg, 0.25 mmol), 2,6-dimethylpiperazine (28.4 mg, 0.25 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.75 mg, 9.94 µmol), diacetoxypalladium (1.116 mg, 4.97 µmol) and cesium carbonate (162 mg, 0.50 mmol) were suspended in 1,4-dioxane (2 mL) . The reaction was purged with nitrogen and heated to 140 °C for 6 hours in an oil bath. Control LC/MS : no traces of expected product.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)N)OC;aryl halide:CC1=CN=C(N=C1C2=CN(C3=CC=CC=C32)S(=O)(=O)C4=CC=CC=C4)Cl, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=CN=C(N=C1C2=CN(C3=CC=CC=C32)S(=O)(=O)C4=CC=CC=C4)NC5=C(C=C(C=C5)N6CCN(CC6)C(=O)C)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Cesium carbonate (2.55 g, 7.82 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.301 g, 0.52 mmol) and diacetoxypalladium (0.058 g, 0.26 mmol) were added to a stirred suspension of 3-(2-chloro-5-methylpyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole (2 g, 5.21 mmol) and 1-(4-(4-amino-3-methoxyphenyl)piperazin-1-yl)ethanone (1.299 g, 5.21 mmol) in 1,4-dioxane (50 ml). The resulting suspension was degassed with argon and stirred at 90 °C for 2 hours. After cooling, the mixture was filtered through a pad of Dicalite speed plus and washed with dichloromethane. The solvent were evaporated. PBO-01132-93-01 The crude product was purified by flash chromatography on silica gel (Merck cartrige SVP D40 - SI60 16-40µm - 90g) eluting with 0 up to 100% EtOAc in dichloromethane . The 1-(4-(3-methoxy-4-(5-methyl-4-(1-(phenylsulfonyl)-1H-indol-3-yl)pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone (1.760 g, 56.6 %) was obtained as a yellow oil. PBO-01132-93-02 An impure batch was obtained. PBO-01132-93-03

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC=C(C=C2)Br;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is optimization. Tris(dibenzylideneacetone)dipalladium(0) (4.5 mg, 4.91 µmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (5.1 mg, 8.81 µmol) were dissolved in dioxane (1.8 mL) in a 10 mL Schlenk tube and activated at 100 °C for 6 min under argon. Then 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (51 mg, 0.18 mmol), 4-(4-bromobenzyl)morpholine (51 mg, 0.20 mmol) and Cesium carbonate (94 mg, 0.29 mmol) were added. It was degassed again and stirred at 100 °C under argon. The reaction was followed by HPLC. After 26 h 85.5 % conversion was obtained. 20 % by-product formation was detected. Finally, the reaction mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC=C(C=C2)Br, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (0.494 g, 0.54 mmol) and9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.375 g, 0.65 mmol) were dissolved in toluene (160 mL) in a 1 L reactor equipped with a condensor and activated at 100 °C for 6 min under argon. Then 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (9.98 g, 36 mmol), 4-(4-bromobenzyl)morpholine (9.48 g, 37 mmol), Sodium tert- pentoxide (6.34 g, 57.60 mmol) and toluene (200 mL) were added. The reaction mixture became sticky yellowish green. It was stirred at 100 °C under argon. The reaction was followed by HPLC. After 3 h no conversion was obtained. The mixture was stirred overnight but the conversion did not move. Then the mixture was cooled to 50 ºC, Pd-complex (5 mol%) and Xantphos (6 mol%) as preactivated catalyst in toluene (100 ml) were added to the mixture, it was degassed carefully, then it was put under argon. Then the reaction mixture was heated at 100 ºC. After 1 h full conversion was detected. The reaction mixture was cooled to room temperature, diluted with dichloromethane (600 mL), extracted with water (4*500 mL), washed with brine (1*500 mL) and dried over Na2SO4. Filtration and concentration afforded orange brown solid. This solid was slurried in EtOAc ( 50 mL) and stirred at reflux point (78 °C) for 10 min. Then it was cooled to room temperature with stirring and filtered. The filtercake was washed with _n_ -pentane (80 mL). Orange filtercake was obtained which still had some impurity. The above obtained orange filtercake was slurried in EtOAc (80 mL) and stirred at 80 °C for 30 min. Then it was cooled to room t emperature and the precipitation was filtered. Yellow fine powder was obtained.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC=C(C=C2)Br, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CCC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (1.703 g, 1.86 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (2.58 g, 4.46 mmol) were dissolved in toluene (50 ml) in a 500 mL two-necked round-bottomed flask equipped with a condensor and activated at 50 °C for 40 min under argon. 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (12.84 g, 46.30 mmol), 4-(4-bromobenzyl)morpholine (13.64 g, 53.25 mmol), Sodium tert-pentoxide (8.16 g, 74.09 mmol) and extra toluene (250 mL) were added. The total volume of the reaction mixture was deoxygenized carefully by switching vacuum-argon 10-times and heated to 110 °C under argon. After 10 min the mixture turned into green. The reaction was monitored by HPLC, after 22 h only ca 65 %. The reactuion was stopped and the mixture was cooled to room temperature. Toluene was removed in vacuo. The residual was dissolved in dichloromethane ( 1.2 L) and extracted with water (2*1 L). The aqueous phase was extracted with EtOAc(600 mL). The combined orange organic phases were filtered through a celitepad and concetrated in vacuo. Dark orange brown sticky gum was obtained which solidified over 2 weeks. This solid was slurried in EtOAc (60 mL) at reflux point for 1 h, then it was cooled to rt slowly with vigorous stirring. Filtration afforded a light yellow solid and an orange filtrate. 0.5 g of the filtercake was purified by preparative HPLC, it afforded 303 mg light yellow solid which was submitted to PARD directly (EN01460-38-001). 1.8 g of the filtercake was purified by preparative HPLC, it afforded 1.02 g light yellow solid and 1.015 g was submitted to PARD directly in a standard bascoded bottle (EN01460-38-002) (barcode: 30152995). The residual material was used for recrystallization studies in the RSL group.

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC=C(C=C2)Br;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Solvent:CCCCOC(=O)C;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CCC(C)(C)[O-].[Na+], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (4.5 mg, 4.91 µmol) and 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (4.38 mg, 9.20 µmol) were dissolved in butyl acetate (1.8 mL) in a 10 mL Schlenk tube and activated at 100 °C for 6 min under argon. Then 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (51 mg, 0.18 mmol), 4-(4-bromobenzyl)morpholine (49.5 mg, 0.19 mmol) and Sodium tert-pentoxide (32.4 mg, 0.29 mmol) were added. It was degassed again and stirred at 100 °C under argon. The reaction was followed by HPLC. After 4.5 h no conversion was observed. Hence the whole reaction mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC=C(C=C2)Br, Reagents are:Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (0.049 g, 54 µmol) and9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.037 g, 0.06 mmol) were dissolved in toluene (15 mL) in a 50 mL two-necked round-bottomed flask equipped with a condensor and activated at 100 °C for 6 min under argon. Then 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (0.998 g, 3.6 mmol), 4-(4-bromobenzyl)morpholine (0.968 g, 3.78 mmol), Sodium tert-pentoxide (0.634 g, 5.76 mmol) and toluene (20 mL) were added. The reaction mixture became sticky yellowish green maybe by addition of the base. It was degassed carefully and stirred at 100 °C under argon. In 1 hour the sticky mixture turned from yellowish green into orange brown muddy mixture. The reaction was followed by HPLC. After 22 h 98 % conversion was obtained. Then it was cooled to rt and filtered. The obtained dark brown crapy filtercake was discarded. The brown filtrate was diluted with dichloromethane (80 mL), extracted with water (3*100 mL), washed with brine (1*100 mL) and dried over Na2SO4. Filtration and concentration afforded orange solid (1.400 g). To this orange solid EtOAc (7 mL) was added and heat to 80 ºC. At 60 ºC it started to form light precipitation. Extra EtOAc (10 mL) was added and stirred at 80 ºC for 10 min. Then it was cooled to rt with a continuous stirring. The light precipitation was filtered off, washed with EtOAc (7 mL) and _n_ -pentane (15 mL), and dried in vacuo. Light yellow powder was obtained.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N;aryl halide:C1COCCN1CC2=CC=C(C=C2)Br, Reagents are:Solvent:CC1=CC=CC=C1;Base:CCC(C)(C)[O-].[Na+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (1.786 g, 1.95 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (1.354 g, 2.34 mmol) were dissolved in toluene (40 mL) in a 100 mL two-necked round-bottomed flask equipped with a condensor and activated at 50 °C for 30 min under argon. In a 2 L reactor 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (36.0 g, 130 mmol), 4-(4-bromobenzyl)morpholine (34.8 g, 136 mmol), Sodium tert-pentoxide (22.91 g, 208.00 mmol) were dissolved in degassed toluene (960 mL) by heating at 100 °C. The preactivated catalyst solution was added to the mixture. It was put under nitrogen atmosphere carefully and stirred at 100 °C. The reaction was monitored by HPLC. After 20 h 38 % conversion was obtained. An extra batch of preactivated catalyst (3 %) in toluene (40 mL) was added and the mixture was stirred at 100 °C under nitrogen. After 52 h 92 % conversion was detected. Then the reaction mixture was cooled to room temperature, diluted with DCM (8 L) and extracted with water (3*5L). The separated organic phase was washed with brine and dried over Na2SO4. Filtration and concentration afforded orange solid which was slurried in EtOAc (100 mL) and stirred at reflux point for 30 min. Then it was cooled to room temperature and filtered. Yellow filtercake was obtained which was washed with EtOAc (150 ml). It was reslurried in EtOAc (100 mL) and stirred at reflux point for 30 min. Then it was cooled to room temperature and filtered. The filtercake was washed with EtOAc (150 ml) and dried in vacuo. Light yellow fine powder was obtained.

Here is a chemical reaction formula: Reactants are:aryl halide:C1COCCN1CC2=CC=C(C=C2)Br;amine:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)N, Reagents are:Base:CCC(C)(C)[O-].[Na+];metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1=NC=C(N1C2CCOCC2)C3=NC(=NC=C3F)NC4=CC=C(C=C4)CN5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The aim of the reaction is only optimization and test. The reaction described below was carried out under argon atmosphere. Palladium(II) acetate (2.245 mg, 10.00 µmol) and (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (5.61 mg, 10.00 µmol) were mixed in DME (0.2 mL) in a 1.4 ml vial under argon and stirred for 1 minute at room temperature. The orange pre-mixed Pd-catalyst solution were added to a 10 mL Schlenk-tube containing 4-(4-bromobenzyl)morpholine (0.282 g, 1.1 mmol) and Sodium tert- pentoxide (0.161 g, 1.46 mmol) in DME (1.5 mL). Finally, 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (0.277 g, 1 mmol) was added and the bright orange reaction mixture was stirred at 90 °C. The mixture turned from bright orange into bright yellow in 1 h. The reaction was followed by HPLC. No reaction took place, hence the mixture was discarded.

Here is a chemical reaction formula: Reactants are:amine:CC1=C(C(=NN1C)C)N;aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC1=C(C(=NN1C)C)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol), 1,3,5-trimethyl-1H-pyrazol-4-amine (76 mg, 0.61 mmol), cesium carbonate (119 mg, 0.36 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.1 mg, 0.05 mmol) and diacetoxypalladium (5.45 mg, 0.02 mmol) were suspended in dioxane (1.5 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 18 hours. Reaction was filtered. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford N-methyl-2-(5-(trifluoromethyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)benzamide (31.0 mg, 24.43 %) as a pale yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl;amine:CC1=NN(C=C1N)C, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)Cl)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1,3-dimethyl-1H-pyrazol-4-amine (180 mg, 1.62 mmol), 2-(2,5-dichloropyridin-4-ylamino)-N-methylbenzamide (400 mg, 1.35 mmol), Sodium t-Butoxide (156 mg, 1.62 mmol),(R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T- BUTYLPHOSPHINE (73.8 mg, 0.14 mmol) and diacetoxypalladium (24.26 mg, 0.11 mmol) were suspended in DME (8 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. Incomplete reaction, the reaction was heated to 150 °C for a further 1 hour in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness. The crude product was then purified by Basic prep HPLC, fractions containing the desired compound were evaporated to dryness to afford 2-(5-chloro-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-N-methylbenzamide (267 mg, 53.3 %) as a brown solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)I;amine:COC1=C2C(=CC=C1)SC(=N2)N, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:COC1=C2C(=CC=C1)SC(=N2)NC3=CC=CC=C3, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 4-methoxybenzo[d]thiazol-2-amine (0.216 g, 1.20 mmol), iodobenzene (0.112 mL, 1.00 mmol), XANTPHOS (0.058 g, 0.10 mmol), Pd2(dba)3 (0.027 g, 0.03 mmol) and SODIUM TERT-BUTOXIDE (0.192 g, 2.00 mmol) placed in a sealed reaction via under an atmosphere of nitrogen and heated at 90ºC for 1 hour. LC/MS indicated mainly product, little SM. Cooled, diluted DCM and washed with water and brine. Org phase dried/MgSO4, filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with dichloromethane. Pure fractions were evaporated to dryness to afford 4-methoxy-N- phenylbenzo[d]thiazol-2-amine (0.039 g, 15.22 %) as an colorless solid. EN01327-44-1 (0.039 g, 0.15 mmol, 15.22 %) Not sure why yield so low, crude lc/ms looked fine. Reaction left for several days before working up.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC2=NC=CC(=C2C=C1Cl)Cl;amine:CC(C)(C)OC(=O)NC1CCNCC1, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC(=O)N(C)C, and Products are 0:C1CN(CCC1N)C2=C3C=C(C=CC3=NC=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (5.60 mg, 0.02 mmol) was added in one portion to tert-butyl piperidin-4-ylcarbamate (100 mg, 0.50 mmol), 4,6-dichloroquinoline (89 mg, 0.45 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.9 mg, 0.05 mmol) and cesium carbonate (488 mg, 1.50 mmol) in DMA (5 mL). The resulting mixture was stirred at 150 °C for 1 hour. LCMS analysis showed formation of a small amount of the desired product. The mixture was heated for a further 2 hours, after which time LCMS analysis showed loss of this small peak. Abandoned.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CC(C1)OC2=CC(=C(C=C2)N)OC;aryl halide:C1=CC2=NC=C(N2C=C1)C3=NC(=NC=C3Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC1=C(C=CC(=C1)OC2CNC2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC=C5)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3-(2,5-dichloropyrimidin-4-yl)imidazo[1,2-a]pyridine (100 mg, 0.38 mmol) _,_ tert-butyl 3-(4-amino-3-methoxyphenoxy)azetidine-1-carboxylate (111 mg, 0.38 mmol) _,_ CESIUM CARBONATE (246 mg, 0.75 mmol) _,_ diacetoxypalladium (3.39 mg, 0.02 mmol) _and_ 9,9-DIMETHYL-4,5-BIS(DIPHENYLPHOSPHINO)XANTHENE (17.46 mg, 0.03 mmol) ___were_ ___suspended_ _in_ 1,4-dioxane (1 ml) _and degased with argon.The reaction was heated from 60°C to 105°C for 3 hours.Doubt about the LCMS,deprotection of the BOC with TFA to confirm the dialkylation._ No good product

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=CC=C(C=C1)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CC=C(C=C1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (0.303 g, 1.35 mmol) was added in one portion to a degassed mixture of 2,4-dichloropyridine (10 g, 67.57 mmol), aniline (6.29 g, 67.57 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.173 g, 2.03 mmol) and cesium carbonate (44.0 g, 135.14 mmol) in dioxane (250 mL) under argon. The resulting mixture was stirred at 100 °C for 24 hours. The mixture was then cooled to room temperature, filtered and concentrated to dryness to give the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-phenylpyridin-2-amine (7.72 g, 55.8 %) as a pale orange solid.

Here is a chemical reaction formula: Reactants are:amine:CN1C(=CC=N1)N;aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)NC3=CC=NN3C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol), 1-methyl-1H-pyrazol-5-amine (58.9 mg, 0.61 mmol), cesium carbonate (119 mg, 0.36 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.1 mg, 0.05 mmol) and diacetoxypalladium (5.45 mg, 0.02 mmol) were suspended in dioxane (1.5 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 18 hours. Reaction was filtered. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford N-methyl-2-(2-(1-methyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)benzamide (62.0 mg, 52.4 %) [salt] as a pale orange solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I;amine:CNC(=O)C1=CC=CC=C1N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (4.305 g, 14.00 mmol), 2-amino-N- methylbenzamide (2.103 g, 14.00 mmol), diacetoxypalladium (0.251 g, 1.12 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.296 g, 2.24 mmol) and cesium carbonate (5.47 g, 16.80 mmol) were mixed together in dioxane (80 mL). Reaction was degassed with argon and was stirred at 90 °C overnight (15 hours) under argon. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 40% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (3.39 g, 73.4 %) as a white crystalline solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I;amine:CNC(=O)C1=CC=CC=C1N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (7 g, 22.77 mmol), 2-amino-N- methylbenzamide (3.42 g, 22.77 mmol), diacetoxypalladium (0.409 g, 1.82 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.108 g, 3.64 mmol) and cesium carbonate (8.90 g, 27.32 mmol) were mixed together in dioxane (140 mL). Reaction was degassed with nitrogen and was stirred at 90 °C overnight under nitrogen. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (5.06 g, 67.4 %) as a pale yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I;amine:CNC(=O)C1=CC=CC=C1N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (500 mg, 1.63 mmol), 2-amino-N- methylbenzamide (244 mg, 1.63 mmol), diacetoxypalladium (29.2 mg, 0.13 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (151 mg, 0.26 mmol) and cesium carbonate (636 mg, 1.95 mmol) were mixed together in dioxane (10 mL). Reaction was degassed with nitrogen and was stirred at 90 °C overnight under nitrogen. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (340 mg, 63.4 %) as a pale yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1C(F)(F)F)Br;amine:CC(C)(C)OC(=O)N1CCC(CC1)(CN=C(C2=CC=CC=C2)C3=CC=CC=C3)C(=O)N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(C)(C)OC(=O)N1CCC(CC1)(CN=C(C2=CC=CC=C2)C3=CC=CC=C3)C(=O)NC4=NC=CC(=C4)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: tert-butyl 4-carbamoyl-4-((diphenylmethyleneamino)methyl)piperidine-1-carboxylate (500 mg, 1.19 mmol), 2-bromo-4-(trifluoromethyl)pyridine (268 mg, 1.19 mmol), and cesium carbonate (541 mg, 1.66 mmol) were suspended in dioxane (2 mL) . The reaction was purged with nitrogen for 10 minutes then 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (30.9 mg, 0.05 mmol) and palladium(II) acetate (7.99 mg, 0.04 mmol) were added. The reaction was heated at 90 °C for 48 hours. The reaction was cooled to room temperature, diluted with DCM, filtered and concentrated. The crude product was purified by flash silica chromatography, elution gradient 0 to 40% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-((diphenylmethyleneamino)methyl)-4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)piperidine-1-carboxylate (480 mg, 71.4 %) as a white solid.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCNCC1;aryl halide:CC1=C(C=CC=C1Br)[N+](=O)[O-], Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=CC=C1[N+](=O)[O-])N2CCN(CC2)C(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1-bromo-2-methyl-3-nitrobenzene (500 mg, 2.31 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (201 mg, 0.35 mmol) and cesium carbonate (1131 mg, 3.47 mmol) and diacetoxypalladium (52.0 mg, 0.23 mmol) were dissolved in toluene (10 mL) and sealed into a microwave tube degazed and purged with argon. The reaction was heated to 100 °C, over a period of 12 hours. The reaction mixture was cooled down to room temperature, filtered and the residue was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. The solvent was evaporated to dryness to afford 1-(4-(2-methyl-3-nitrophenyl)piperazin-1-yl)ethanone (600 mg, 98 %) as a solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CNC(=O)C1=C(C=CC(=C1)F)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=C(C=CC(=C1)F)NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: palladium acetate (31.2 mg, 0.14 mmol) was added to 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (121 mg, 0.21 mmol), Cesium carbonate (2266 mg, 6.95 mmol), 2-amino-5-fluoro-N-methylbenzamide (585 mg, 3.48 mmol) and 2,5-dichloro-4-iodopyridine (1000 mg, 3.65 mmol) in dioxane (20 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18hrs then cooled. Product appeared to be out of solution. Product and bis product suggested. Disappointing! The reaction mixture was evaporated to dryness and redissolved in EtOAc (100 mL), and washed sequentially with saturated Na2CO3 (50 mL), water (50 mL), and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford desired product as an beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1CCC(CC1)NC(=O)C2=CN=C(C=C2)Cl;amine:C1=CC(=CC=C1C#N)N, Reagents are:Base:CC(C)(C)[O-].[K+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:C1CCC(CC1)NC(=O)C2=CN=C(C=C2)NC3=CC=C(C=C3)C#N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: In a 50 mL round-bottomed flask a TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.115 g, 0.13 mmol),POTASSIUM TERT-BUTOXIDE (0.282 g, 2.51 mmol)and BINAP (0.157 g, 0.25 mmol) in dry 1,4-dioxane (10 mL) was mixed under N2.Followed by 6-chloro-N-cyclohexylnicotinamide (.300 g, 1.26 mmol) and 4-aminobenzonitrile (0.178 g, 1.51 mmol) was added and resulting mixture(dark brown) was heated at 100oC for 3 hrs.LCMS analysis showed the formation of required product.Reaction stopped,crude was passed through celite and washed with dioxane and finally with methanol.The filtrate was dried and dissolved in 3 ml DMSO for Waters MS Purification system.Pure fractions collected and concentrated.A White solid obtained as a product 6-(4-cyanophenylamino)-N-cyclohexylnicotinamide (0.040 g, 9.93 %).32 mg of above product was submitted for MGyrx2 projetct.LCMS/NMR confirmed the product.

Here is a chemical reaction formula: Reactants are:amine:CC1=NN(C=C1N)C;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (7.79 mg, 0.03 mmol), (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (19.46 mg, 0.03 mmol), Cesium carbonate (0.032 mL, 0.40 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (38.6 mg, 0.35 mmol) and 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methoxybenzamide (100 mg, 0.29 mmol) were suspended in DME (2.5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product as a orange gum. The sample was given to the purification group to be purified by preparative HPLC. Fractions containing the desired compound were evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methoxybenzamide (13.60 mg, 11.18 %) as a tan gum. The sample was not pure enough to register so will be re-made.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(N=C1Cl)Cl;amine:C1CC2=CC=CC=C2NC1, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:C1CC2=CC=CC=C2N(C1)C3=NC(=NC=C3)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,4-dichloropyrimidine (200 mg, 1.34 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (78 mg, 0.13 mmol), Tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) and Cesium carbonate (656 mg, 2.01 mmol) was added to a microwave vial. toluene (2 mL) was added. 1,2,3,4-tetrahydroquinoline (179 mg, 1.34 mmol) was added. Heated to 120ºC in microwave oven for 90min. Crude filtered through celite and then added to prepHPLC. 30-70% acetonitrile in water. Pure fractions pooled and then freezedried over night. Yielded 1-(2-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroquinoline (24.00 mg, 7.28 %)

Here is a chemical reaction formula: Reactants are:aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl;amine:CC1=NN(C=C1N)C, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (8.17 mg, 0.04 mmol), (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (20.40 mg, 0.04 mmol), Sodium tert-butoxide (0.052 mL, 0.42 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (40.5 mg, 0.36 mmol) and 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol) were suspended in DME (2.5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (41.3 mg, 33.7 %) as a orange gum. The sample was given to the purification group to be purified by preparative HPLC. Fractions containing the desired compound were evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (41.3 mg, 33.7 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:C1COC(=O)N1;aryl halide:C1=CC(=CC=C1C#N)C2=CSC(=N2)Br, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1COC(=O)N1C2=NC(=CS2)C3=CC=C(C=C3)C#N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 4-(2-bromothiazol-4-yl)benzonitrile (100 mg, 0.38 mmol), 2-Oxazolidinone (49.3 mg, 0.57 mmol), diacetoxypalladium (5.93 mg, 0.03 mmol), cesium carbonate (369 mg, 1.13 mmol), water (10 µl) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (21.82 mg, 0.04 mmol) were suspended in dioxane (2 mL), thoroughly degassed and sealed into a microwave tube and stirred at RT for 20 mins. The reaction was then heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. Load of rubbish... ABANDONED

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=NN(C=C1N)C.Cl.Cl;amine:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C=CC(=C3)F)C(=O)NC)Cl)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide (165 mg, 0.53 mmol), 1,3-dimethyl-1H-pyrazol-4-amine dihydrochloride (193 mg, 1.05 mmol), cesium carbonate (376 mg, 1.16 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (48.6 mg, 0.08 mmol) and diacetoxypalladium (9.43 mg, 0.04 mmol) were suspended in dioxane (3 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 16 hours => _reaction not complete._ (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine), diacetoxypalladium and cesium carbonate were added. The reaction was degased, purged with nitrogen and heated to 110 °C for 4 hours => _reaction still not complete, no progress ..._ Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 1% acetic acid) and acetonitrile as eluent. The pure fractions were combined, basified with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2. Organic layer was washed with brine, dried over MgSO4 and concentrated to dryness to afford 2-(5-chloro-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (8.00 mg, 3.92 %) as a green dry film.

Here is a chemical reaction formula: Reactants are:amine:C1OC2=CC=CC(=C2O1)N;aryl halide:C1CC1C(=O)NC2=NC=CC(=C2)Cl, Reagents are:Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=CC=C3)OCO4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: benzo[d][1,3]dioxol-4-amine (100 mg, 0.73 mmol), N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (143 mg, 0.73 mmol), XANTPHOS (50.6 mg, 0.09 mmol), PALLADIUM(II) ACETATE (8.19 mg, 0.04 mmol) and CESIUM CARBONATE (475 mg, 1.46 mmol) were suspended in DMA (3mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 1.5 hours in the microwave reactor and cooled to RT. LC/MS showed completion. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and pure fractions were evaporated to dryness to afford N-(4-(benzo[d][1,3]dioxol-4-ylamino)pyridin-2-yl)cyclopropanecarboxamide as a brown oil. The crude product was purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(4-(benzo[d][1,3]dioxol-4-ylamino)pyridin-2-yl)cyclopropanecarboxamide (110 mg, 50.7 %) as a cream solid.

Here is a chemical reaction formula: Reactants are:amine:CN1CCNCC1;aryl halide:COC(=O)C1=CC=C(C=C1)OCC2=C(C=CC=N2)Br, Reagents are:Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CN1CCN(CC1)C2=C(N=CC=C2)COC3=CC=C(C=C3)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of methyl 4-((3-bromopyridin-2-yl)methoxy)benzoate (360 mg, 1.12 mmol), Pd2dba3 (205 mg, 0.22 mmol), BINAP (278 mg, 0.45 mmol), cesium carbonate (728 mg, 2.23 mmol) and 1-methylpiperazine (168 mg, 1.68 mmol) in DMA (10 mL) was stirred at 100 °C for overnight. Sat. NaHCO3 aq was added to the mixture, extracted with ethyl acetate three times, the combined organics were dried over anhydrous Na2SO4, filtered, the filtrate was conc. in vacuo, the residue was purified with ISCO (50% ethyl acetate in hexant to 100% ethyl acetate to 40% mthanol in ethyl acetate) to yield a brown oil as methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate (245 mg, 64.2 %).

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1Cl)Br)C#N;amine:CN(C)[C@H]1CCNC1, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)[C@H]1CCN(C1)C2=C(C=CC(=C2)Cl)C#N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 2-bromo-4-chlorobenzonitrile (500 mg, 2.31 mmol), (S)-N,N-dimethylpyrrolidin-3-amine (317 mg, 2.77 mmol), cesium carbonate (1505 mg, 4.62 mmol), tris(dibenzylideneacetone)dipalladium(0) (212 mg, 0.23 mmol) and BINAP (288 mg, 0.46 mmol) in toluene (15 mL) was stirred at 100 °C for overnight. Conc. in vacuo, the residue was purified with ISCO (100% ethyl acetate to 30% methanol in ethyl acetate) to yield a light yellow solid as (S)-4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)benzonitrile (400 mg, 69.3 %).

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)Cl)C#N)C;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C#N)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (35.6 mg, 0.20 mmol), 4-chloro-6-(1,3-dimethyl-1H-pyrazol-4-ylamino)nicotinonitrile (25 mg, 0.10 mmol), diacetoxypalladium (1.133 mg, 5.05 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.84 mg, 10.09 µmol) and cesium carbonate (39.5 mg, 0.12 mmol) were dissolved in dioxane (0.5 mL) and sealed into a microwave tube. nitrogen was let to bubble into the mixture then the reaction was heated to 100 °C for 90 minutes. Crude LCMS showed the expected product P3 and no hydrolysis by-product at all like in _EN01775-20_ !! The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. **10 days later** , the fractions containing the desired compound were evaporated to dryness to afford impure 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (13.00 mg, 33.2 %): it has probably gone off after 10 days in solution (aqueous ammonium carbonate and acetonitrile) ENCOURAGING, THOUGH.

Here is a chemical reaction formula: Reactants are:amine:COC1=C(C=CC(=C1)N2CCOCC2)N;aryl halide:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCOCC4)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2-methoxy-4-morpholinoaniline (158 mg, 0.76 mmol), 2-(2,5-dichloropyridin-4-ylamino)-N-methylbenzamide (150 mg, 0.51 mmol),diacetoxypalladium (5.69 mg, 0.03 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (29.3 mg, 0.05 mmol) and cesium carbonate (330 mg, 1.01 mmol) were weighed out in a microwave vial and sealed. dioxane (3 mL) was added and argon was let to bubble for 5 minutes at rt. The resulting mixture was stirred at 110 °C for 1 hour. The reaction mixture was allowed to cool to room temperature and concentrated in presence of decalite speed plus. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness. The foam was triturated in terbutyl methyl ether and the resulting precipitate was collected by filtration and washed with tBuOMe to afford 2-(5-chloro-2-(2-methoxy-4-morpholinophenylamino)pyridin-4-ylamino)-N-methylbenzamide (193 mg, 81 %) as a pale pink solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=CC(=C1)F)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC1=C(C=CC(=C1)F)N2CCN(CC2)C(=O)OC(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: In a 200ml flask was added 1-bromo-4-fluoro-2-methylbenzene (2 g, 10.58 mmol) and TERT-BUTYL 1-PIPERAZINECARBOXYLATE (2.365 g, 12.70 mmol), CESIUM CARBONATE (5.17 g, 15.87 mmol) , BINAP (0.791 g, 1.27 mmol) 18-CROWN-6 (0.336 g, 1.27 mmol), followed by toluene (25 ml). Degass the mixture. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.581 g, 0.63 mmol) was added. Heat at 110oC under nitrogen in an oil bath for overnight. The reaction mixture was diluted with ethyl acetate and filtered through celite. The Celite was washed with EtOAC. The EtOAC was concentrated down to give a brown oil. The crude product was purified by silica gel column(40g) and was eluted with 0% EtOAC/Hexane -50% EtOAC/Hexane. Yield: 0.5g Yellow oil.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:C1=CC(=C(C=C1F)C(F)(F)F)Br, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=C(C=C(C=C2)F)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: In a 100ml sealtube was added 1-bromo-4-fluoro-2-(trifluoromethyl)benzene (0.91 g, 3.63 mmol), CESIUM CARBONATE (1.775 g, 5.45 mmol), CESIUM CARBONATE (1.775 g, 5.45 mmol), BINAP (0.271 g, 0.44 mmol), TERT-BUTYL 1-PIPERAZINECARBOXYLATE (0.812 g, 4.36 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.200 g, 0.22 mmol) and 18-CROWN-6 (0.115 g, 0.44 mmol). Followed by 15mL toluene. The mixture was degassed by N2 bubbling for 15min. The reaction mixture was heated at 110oC under nitrogen in an oil bath for overnight. The reaction mixture was diluted with ethyl acetate and filtered through celite. The Celite was washed with EtOAC. The EtOAC was concentrated down to give a brown oil. The crude product was purified by silica gel column(40g) and was eluted with 0% EtOAC/Hexane -25% EtOAC/Hexane. Yield: 0.93g Yellow oil. .

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CC2CNCC(C1)O2;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+], and Products are 0:CC(=O)N1CC2CN(CC(C1)O2)C3=CC(=C(C=C3)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)ethanone (36.3 mg, 0.21 mmol), 4-bromo-1-methoxy-2-nitrobenzene (45 mg, 0.19 mmol), diacetoxypalladium (4.35 mg, 0.02 mmol), biphenyl-2-yldicyclohexylphosphine (10.88 mg, 0.03 mmol) and potassium phosphate (61.8 mg, 0.29 mmol) in DME (0.5 mL) were degassed with nitrogen and stirred at 80 °C overnight => _no product formed, degradation_ **_ABANDONED_**

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C(=NC(=N1)N)Cl)CC2=CC=C(C=C2)CC#N;amine:CCC[C@@H](CO)N, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CCC[C@@H](CO)NC1=NC(=NC(=C1CC2=CC=C(C=C2)CC#N)C)N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (8.23 mg, 0.04 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (42.4 mg, 0.07 mmol) were added to dioxane (3 mL) and the solution was stirred at room temperature for 10 minutes. 2-(4-((2-amino-4-chloro-6-methylpyrimidin-5-yl)methyl)phenyl)acetonitrile (200 mg, 0.73 mmol), (S)-(+)-2-Amino-1-pentanol (151 mg, 1.47 mmol) and POTASSIUM CARBONATE (203 mg, 1.47 mmol) were added and the mixture was heated at 100 °C for 15 hours. LCMS showed no product and reaction not progressed.

Here is a chemical reaction formula: Reactants are:amine:CC[C@H]1CNC(=O)O1;aryl halide:CC1=C(C(=NC(=N1)/N=C/N(C)C)Cl)CC2=CC=C(C=C2)CC#N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[K+].[K+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC[C@H]1CN(C(=O)O1)C2=NC(=NC(=C2CC3=CC=C(C=C3)CC#N)C)/N=C/N(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (8.22 mg, 0.04 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (42.4 mg, 0.07 mmol) were added to dioxane (3 mL) and the solution was stirred at room temperature for 10 minutes.(E)-N'-(4-chloro-5-(4-(cyanomethyl)benzyl)-6-methylpyrimidin-2-yl)-N,N-dimethylformimidamide (240 mg, 0.73 mmol), (S)-5-ethyloxazolidin-2-one (169 mg, 1.46 mmol) and POTASSIUM CARBONATE (202 mg, 1.46 mmol) were added and the mixture was heated at 100 °C for 1 hour. The solvent was evaporated under reduced pressure and the crude product was purified by flash silica chromatography, elution gradient 2 to 5% methanol in dichloromethane. Pure fractions were evaporated to dryness to afford (S,E)-N'-(5-(4-(cyanomethyl)benzyl)-4-(5-ethyl-2-oxooxazolidin-3-yl)-6-methylpyrimidin-2-yl)-N,N-dimethylformimidamide (136 mg, 45.7 %) as a colorless solid.

Here is a chemical reaction formula: Reactants are:amine:CNC(=O)C1=C(C=C(C=C1)F)N;aryl halide:C1=C(C(=CN=C1Cl)Cl)I, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (6.15 mg, 0.03 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (150 mg, 0.55 mmol), 2-amino-4-fluoro-N- methylbenzamide (92 mg, 0.55 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (31.7 mg, 0.05 mmol) and cesium carbonate (268 mg, 0.82 mmol) in 1,4-dioxane (2.5 mL) under nitrogen. The resulting suspension was stirred at 100 °C for 16 hours. The mixture was cooled to RT; filtered the solvent was evaporated. The crude product was absorbed on silica gel and purified by flash chromatography on silica gel eluting with 20 to 80% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide (60.0 mg, 34.9 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CNC(=O)C1=C(C=C(C=C1)F)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,5-dichloro-4-iodopyridine (250 mg, 0.91 mmol), 2-amino-4-fluoro-N- methylbenzamide (169 mg, 1.00 mmol) diacetoxypalladium (10.25 mg, 0.05 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (52.8 mg, 0.09 mmol) and cesium carbonate (446 mg, 1.37 mmol) were dissolved in 1,4-dioxane (2.5 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 140 °C over a period of 30 minutes in the microwave reactor. The mixture was cooled to RT; filtered the solvent was evaporated. The crude product was absorbed on silica gel and purified by flash chromatography on silica gel eluting with 20 to 80% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide (175 mg, 61.0 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C(=CN=C1Cl)Cl)I;amine:CNC(=O)C1=C(C=C(C=C1)F)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2Cl)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: palladium acetate (31.2 mg, 0.14 mmol) was added to 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (121 mg, 0.21 mmol), Cesium carbonate (2266 mg, 6.95 mmol), 2-amino-4-fluoro-N-methylbenzamide (585 mg, 3.48 mmol) and 2,5-dichloro-4-iodopyridine (1000 mg, 3.65 mmol) in dioxane (40 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18hrs then cooled. Product and bis product suggested. Disappointing! The reaction mixture was evaporated to dryness and redissolved in EtOAc (150 mL), and washed sequentially with saturated NaHCO3 (2 x 100 mL), water (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered then evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford desired product as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CC2CNCC(C1)O2;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(=O)N1CC2CN(CC(C1)O2)C3=CC(=C(C=C3)OC)[N+](=O)[O-], please give me the reaction condition of this formula.

The condition of this chemical reaction is: 1-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)ethanone (36.3 mg, 0.21 mmol), 4-bromo-1-methoxy-2-nitrobenzene (45 mg, 0.19 mmol), diacetoxypalladium (3.48 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.98 mg, 0.02 mmol) and sodium 2-methylpropan-2-olate (28.0 mg, 0.29 mmol) in dioxane (0.5 mL) were degassed with nitrogen and stirred at 110 °C for 4 hours => _some product formed, by-products are major + degradation_ **_ABANDONED_**

Here is a chemical reaction formula: Reactants are:aryl halide:CS(=O)(=O)C1=CC=C(C=C1)COC2=NC=C(C=N2)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CN=C(N=C2)OCC3=CC=C(C=C3)S(=O)(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyrimidine (1.03 g, 3.00 mmol), tert- butyl piperazine-1-carboxylate (624.6 mg, 3.35 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (154.3 mg, 0.17 mmol),2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (100.0 mg, 0.16 mmol) and sodium 2-methylpropan-2-olate (454.4 mg, 4.73 mmol) were mixed with toluene (20 mL). N2 was bubbled through the solvent for 15 minutes.The resulting mixture was stirred at 80 °C for over night under N2.The reaction mixture was filtered through celite. The reaction mixture was evaporated to dryness and redissolved in EtOAc (75 mL), and washed sequentially with water (2x75 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(methylsulfonyl)benzyloxy)pyrimidin-5-yl)piperazine-1-carboxylate (1.664 %) as a white solid. The product was not pure! The crude product was purified by flash alumina chromatography, elution gradient 0 to 70% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(methylsulfonyl)benzyloxy)pyrimidin-5-yl)piperazine-1-carboxylate (1.664 %) as a white solid. The product was still not pure but was handed in for testing anyway, as 92% pure by NMR.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:CS(=O)(=O)C1=CC=C(C=C1)COC2=NC=C(C=N2)Br, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CN=C(N=C2)OCC3=CC=C(C=C3)S(=O)(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyrimidine (748.8 mg, 2.18 mmol), tert- butyl piperazine-1-carboxylate (447 mg, 2.40 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (100 mg, 0.11 mmol),2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (67.9 mg, 0.11 mmol) and sodium 2-methylpropan-2-olate (315 mg, 3.27 mmol) were mixed with toluene (20 mL). N2 was bubbled through the solvent for 15 minutes.The resulting mixture was stirred at 80 °C for over night under N2.The reaction mixture was filtered through celite. The reaction mixture was evaporated to dryness and redissolved in EtOAc (75 mL), and washed sequentially with water (2x75 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(methylsulfonyl)benzyloxy)pyrimidin-5-yl)piperazine-1-carboxylate (55.0 %) as a yellow solid. Was not pure and tailed on the coloumn. The crude product was purified by preparative HPLC (Phenomenex Gemini C18 110A (axia) column, 5µ silica, 21 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.5% NH3 and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford as a white solid. The product crashed out on the HPLC coloumn and blocked the system, which gave bad recovery. Turns out the product is not stable. 2D TLC shows tailing of product..

Here is a chemical reaction formula: Reactants are:aryl halide:CS(=O)(=O)C1=CC=C(C=C1)COC2=NC=C(C=C2)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CN=C(C=C2)OCC3=CC=C(C=C3)S(=O)(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (48.3 mg, 0.08 mmol) was added in one portion to 5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyridine (257.9 mg, 0.75 mmol), tert-butyl piperazine-1-carboxylate (160.9 mg, 0.86 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (51.1 mg, 0.06 mmol) and sodium 2-methylpropan-2-olate (120.1 mg, 1.25 mmol) in toluene (10 mL). N2 was bubbled through the solvent for 15 minutes.The resulting mixture was stirred at 80 °C for over night under N2.The reaction mixture was filtered through celite. The reaction mixture was evaporated to dryness and redissolved in EtOAc (75 mL), and washed sequentially with water (2x75 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 70% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(6-(4-(methylsulfonyl)benzyloxy)pyridin-3-yl)piperazine-1-carboxylate (42.6 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br;amine:CC(=O)N1CCC2=C1C=CC(=C2)CCN3CCNCC3, Reagents are:Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC5=C(C=C4)N(CC5)C(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 06/05 2009 14:53:56 +0200 To ethyl 7-bromobenzofuran-2-carboxylate (0.460 g, 1.71 mmol) and 1-(5-(2-(piperazin-1-yl)ethyl)indolin-1-yl)ethanone (0.491 g, 1.79 mmol) (from EN02198-74) in dry degassed dioxane (8 mL) were added Cesium carbonate (0.724 g, 2.22 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.081 g, 0.17 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.078 g, 0.09 mmol) under argon and the reaction heated at 95°C overnight. After cooling to rt, water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (MgSO4), filtered and evaporated. The crude was purified by flash (SiO2; DCM/MeOH 95/5) to give 0.485 g (61%) of the product as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:CC(=O)N1CCC2=C1C=CC(=C2)CCN3CCNCC3;aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC5=C(C=C4)N(CC5)C(=O)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 22/04 2009 09:43:42 +0200 To ethyl 7-bromobenzofuran-2-carboxylate (0.095 g, 0.35 mmol) and 1-(5-(2-(piperazin-1-yl)ethyl)indolin-1-yl)ethanone (0.101 g, 0.37 mmol) (from EN02198-74) in dry degassed dioxane (1.5 mL) were added Cesium carbonate (0.150 g, 0.46 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.017 g, 0.04 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.016 g, 0.02 mmol) under argon and the reaction heated at 95°C for 5.5h. After cooling to rt, water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (MgSO4), filtered and evaporated. The crude was purified by flash (SiO2; DCM/MeOH 95/5) to give 0.105 g of the product as a yellow solid.

Here is a chemical reaction formula: Reactants are:amine:C1CN(CCN1)CCC2=CC=CC=N2;aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC=CC=N4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 27/05 2009 13:35:19 +0200 To dry degassed dioxane (30 mL) were added ethyl 7-bromobenzofuran-2-carboxylate (2.30 g, 8.55 mmol) and 1-(2-(pyridin-2-yl)ethyl)piperazine (1.798 g, 9.40 mmol), Cesium carbonate (3.62 g, 11.11 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.407 g, 0.85 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.391 g, 0.43 mmol) under argon and the reaction heated at 95°C for 4h. The reaction mixture was filtered and solvent evaporated. The material was purified by flash (SiO2; DCM/MeOH 97/3) to give 0.620 g, but it was not pure enough (EN02198-94-001). A second flash was performed (SiO2; DCM/MeOH 97/3) to give 0.540 g of the product as a yellow solid (EN02198-94-002). 100% pure according to HPLC. The reaction mixture was combined with the reaction mixture in EN02745-56 and hydrolysed.

Here is a chemical reaction formula: Reactants are:amine:C1CN(CCN1)CCC2=CC=CC=N2;aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC=CC=N4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The reaction mixture of ethyl 7-bromobenzofuran-2-carboxylate (2.0 g, 7.43 mmol), 1-(2-(pyridin-2-yl)ethyl)piperazine (1.564 g, 8.18 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.476 g, 0.52 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.496 g, 1.04 mmol) and Cesium carbonate (3.63 g, 11.15 mmol) in dioxane (30 mL) (degassed with argon for 10 min) was heated at 95 °C under argon for 5 h. After cooling, the reaction mixture was filtered and concentrated. The product was purified twice by isco, the first using DCM:MeOH (0-5%) and the second time using DCM:MeOH (0-3%).

Here is a chemical reaction formula: Reactants are:aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br;amine:C1CN(CCN1)CCC2=CC=CC=N2, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC=CC=N4, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 07/01 2009 12:44:11 +0100 To ethyl 7-bromobenzofuran-2-carboxylate (0.100 g, 0.37 mmol) and 1-(2-(pyridin-2-yl)ethyl)piperazine (0.075 g, 0.39 mmol) in dry degassed dioxane (1.5 mL) were added Cesium carbonate (0.157 g, 0.48 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.018 g, 0.04 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.017 g, 0.02 mmol) under argon and the reaction heated at 95°C o/n. All starting material consumed. Water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (MgSO4), filtered and evaporated. The crude was purified by flash (SiO2; DCM/MeOH 95/5) to give 0.0661 g of the product as a pale yellow semisolid.