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Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=CC(=C1)Cl)I;amine:CN1CCNCC1, 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:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CCN(CC1)C2=C(C=C(C=C2)Cl)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-methylpiperazine (0.021 mL, 0.19 mmol) was added to 4-chloro-1-iodo-2-methoxybenzene (50 mg, 0.19 mmol) and sodium 2-methylpropan-2-olate (35.8 mg, 0.37 mmol) in toluene (0.650 mL) and the solution degassed. rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (11.60 mg, 0.02 mmol) and Palladium II acetate (4.18 mg, 0.02 mmol) were added to the resulting mixture and the vial stirred at 80 °C for 17 hours. LCMS revelead product peak, but not great. Product not isolated. |
Here is a chemical reaction formula: Reactants are:amine:CC1=CSC(=N1)N;aryl halide:C1COCC(=O)N1C2=NC(=CC=C2)Br, 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.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=CSC(=N1)NC2=NC(=CC=C2)N3CCOCC3=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: **_September 24 2015_** 4-methylthiazol-2-amine (200 mg, 1.75 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (450 mg, 1.75 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (450 mg, 1.75 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (81 mg, 0.14 mmol) and cesium carbonate (685 mg, 2.10 mmol) in toluene (15 mL) and DMF (1)were microwaved at 115 °C under N2 for one hour. _(Note: Initially, DMF was not added as co-solvent, the microwave instrument was repeatly failed to reach the temperature, and shut down ar 100 °C. It was due to the low thremal absorbance of toluene. Therefore, DMF was added to improve this situation.)_ LCMS showed no precursors and 87% of the desired mass MH+291 @ 0.87 min on a 2-min basic run. The reaction was cooled to RT. **_September 25 2015_** The reaction mixture was diluted with EtOAc, washed with water, filtered, and evaporated to give a brown solid as the crude product. The crude product was added to a silica gel column, and was eluted with 20-100%EtOAc in Heptane. Collected fractions. Based on TLC and LCMS, most product fractions contained a non-MS-ionization unknown, were combined, and evpoarated to give an orange-yellow solid. The orange-yellow solid was reloaded to a silica gel column and was eluted with 20-100%EtOAc in Heptane . Collected fractions . **_September 28 2015_** Based on TLC and LCMS, the product fractions were combined, and evpoarated to give a pale-yellow solid. Based on LCMS, it was 93% pure; based on NMR, it was 94~95% pure. |
Here is a chemical reaction formula: Reactants are:amine:CC1=CSC(=N1)N;aryl halide:C1COCC(=O)N1C2=NC(=CC=C2)Br, Reagents are:Solvent:CC1=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.[Pd], and Products are 0:CC1=CSC(=N1)NC2=NC(=CC=C2)N3CCOCC3=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: **_September 16 2015_** 4-methylthiazol-2-amine (65 mg, 0.57 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (146 mg, 0.57 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (146 mg, 0.57 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (26.4 mg, 0.05 mmol) and cesium carbonate (223 mg, 0.68 mmol) in toluene (5 mL) were microwaved at 120 °C under N2 for one hour. LCMS showed no precursors and 68% of the desired mass MH+291 @ 0.87 min on a 2-min basic run. The reaction mixture was diluted with EtOAc, washed with water, filtered, and evaporated to give a brown solid as the crude product. **_September 17 2015_** The crude product was added to a Biotage column, and was eluted with 0-10% ammoniated MeOH in DCM. Collected fractions. Based on TLC and LCMS, the product fractions were combined, and evpoarated to give an orange-brown solid (150 mg). Based on LCMS, it was only 89% pure. The orange-brown solid was loaded on a Grace column, and eluted with 20-100%EtOAc in Heptane. Collected fractions. (Note: the solubility of the orange-brown solid was not good, and about 12 mL CH2Cl2 was used to dissolved everything) Based on TLC and LCMS, the product fractions were combined, and evpoarated to give an off-white solid (110 mg). Based on LCMS, it was 100% pure; based on M;R, it was > 95% pure. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NN=C1Cl)Cl;amine:CC(C)(C)OC(=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:C1COCCO1, and Products are 0:CC(C)(C)OC(=O)NC1=NN=CC(=C1)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: **_April 15 2016_** 3,5-dichloropyridazine (1 g, 6.71 mmol), tert-butyl carbamate (3.93 g, 33.56 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (0.583 g, 1.01 mmol), PdOAc2 (0.452 g, 2.01 mmol) and CS2CO3 (4.37 g, 13.43 mmol) in 1,4-dioxane (20 mL) was degassed through recharged with nitrogen, and was heated at 80 °C overnight. **_April 18 2016_** LCMS showed 23% of the precursor @ 0.55 min (no mass ionization) left on a 2-min basic run. GCMS showed no precursor and 94% of an unknown @ 6.90 min (whihc might be the desired product but not ionizable) on a 10-min run. The reaction was cooled to RT. The crude mixture was concentrated to givr a dark-brown gum. The dark-brown gum was dissolved in EtOAc, washed with water, and evaporated to give a brown solid. The brown solid was passed through a 10 g SiO2 flash column eluting with EtOAc, collected all of the eluent, and then evaporated to give a brown solid as the crude. The crude would be used in EN08121-59 without purification, assuming 100% yield. |
Here is a chemical reaction formula: Reactants are:amine:C(CN)N;aryl halide:C1=CC=C(C(=C1)Cl)Br, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];metal and ligand:CC1=CC=C(C=C1)P(C2=CC=C(C=C2)C)C3=CC=C(C=C3)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1=CC=C(C(=C1)NCCN)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Ref: R2239 To a mixture of 1-bromo-2-chlorobenzene (0.824 g, 4.30 mmol), tri-p- tolylphosphine (0.262 g, 0.86 mmol), sodium 2-methylpropan-2-olate (0.414 g, 4.30 mmol), diacetoxypalladium (0.097 g, 0.43 mmol) in toluene (4 mL) was added ethane-1,2-diamine (1.293 g, 21.52 mmol). The mixture was heated with microwave at 140 °C for 1 h. No product was formed. |
Here is a chemical reaction formula: Reactants are:amine:C1CNCCN1;aryl halide:C1=CC2=C(C=C1Br)OC(O2)(F)F, Reagents are:metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[K+], and Products are 0:C1CN(CCN1)C2=CC3=C(C=C2)OC(O3)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 13-May-09 10:32:07 +0100 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (0.500 g, 2.11 mmol), piperazine (0.182 g, 2.11 mmol) and BIS(TRI-T-BUTYLPHOSPHINE)PALLADIUM(0) (0.054 g, 0.11 mmol) and potassium 2-methylpropan-2-olate (0.349 g, 2.95 mmol) were suspended in dioxane (10vol) (10 mL) and heated to 90°C for 1 hour. LC-MS shows no starting material 52% product and 41% dimer. The reaction mixture was combined with EN02263-54 filtered and 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-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)piperazine (0.259 g, 50.7 %) as a yellow oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=NC(=CC=C1)Br;amine:C/C=C(/C1=CC=C(C=C1)Cl)\N(C2=CC=C(C=C2)OC)C(=O)NC, 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:C/C=C(/C1=CC=C(C=C1)Cl)\N(C2=CC=C(C=C2)OC)C(=O)N(C)C3=NC(=CC=C3)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (Z)-1-(1-(4-chlorophenyl)prop-1-enyl)-1-(4-methoxyphenyl)-3-methylurea (0.400 g, 1.21 mmol),2-bromo-6-methoxypyridine (0.292 ml, 2.42 mmol),SODIUM TERT- BUTOXIDE (0.349 g, 3.63 mmol),XANTPHOS (0.070 g, 0.12 mmol) and Pd2(dba)3 (0.055 g, 0.06 mmol) were dissolved intoluene (11.80 ml) and sparged under nitrogen for 1 hour. The resulting mixture was then heated to 110 °C for 48 hours or unitil conversion was complete by TLC. NH4Cl (10 mL) was added and the mixture was extracted twice (EtOAc 20 mL). The organic phases were combined, washed with brine (20 mL), dried (MgSO4) and the solvent removed under reduced pressure. The crude product was then purified by flash column chromatography to give (Z)-1-(1-(4-chlorophenyl)prop-1-enyl)-1-(4-methoxyphenyl)-3-(6-methoxypyridin-2-yl)-3-methylurea (0.381 g, 72.0 %) |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)C#N;amine:CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)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:CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)NC4=CC(=CC(=C4)C#N)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (300 mg, 0.87 mmol), cesium carbonate (1104 mg, 3.39 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (126 mg, 0.22 mmol) and 3-bromo-5-fluorobenzonitrile (382 mg, 1.91 mmol) in degassed 1,4-dioxane (2ml), was added TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (59.7 mg, 0.07 mmol). The suspension was heated in a sealed container up to 85-95°C for 16hours. The reaction mixture was filtered through a short pad of dicalite, concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford the product which still containing some impurities (see UPLC 03441-77-003). The product mixture was then re-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 8-(1-(3-cyano-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (330 mg, 82 %) as a clear white solid. |
Here is a chemical reaction formula: Reactants are:amine:C1=CN=C(N=C1)N;aryl halide:C1=CN=C(C=C1Cl)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:C1=CN=C(N=C1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.061 g, 0.27 mmol) was added to 2,4-dichloropyridine (0.500 g, 3.38 mmol), 2-Aminopyrimidine (0.321 g, 3.38 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.235 g, 0.41 mmol) and Cesium carbonate (2.202 g, 6.76 mmol) in dioxane (15 mL) at 20ºC under nitrogen. The resulting suspension was stirred at 100 °C for 90 minutes. Complete reaction by LCMS, cooled to room temperature. The reaction mixture was then filtered, washed with DCM and filtrate concentrated _in vacuo_ to give a yellow gum. This was then dissolved in DCM (200 mL), washed with water (200 mL) and brine (200 mL). The organic layer was passed through phase separating cartridge and concentrated under reduced pressure. 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 N-(4-chloropyridin-2-yl)pyrimidin-2-amine (0.361 g, 51.7 %) as an off-white solid. |
Here is a chemical reaction formula: Reactants are:amine:C1=CN=C(N=C1)N;aryl halide:C1=CN=C(C=C1Cl)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:C1=CN=C(N=C1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.607 g, 2.70 mmol) was added to 2,4-dichloropyridine (5.00 g, 33.79 mmol), 2-Aminopyrimidine (3.21 g, 33.79 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (2.346 g, 4.05 mmol) and Cesium carbonate (22.02 g, 67.57 mmol) in dioxane (15 mL) at 20ºC under nitrogen. The resulting suspension was stirred at 100 °C for 90 minutes. Complete reaction by LCMS, cooled to room temperature. The reaction mixture was then filtered, washed with DCM and filtrate concentrated _in vacuo_ to give a yellow gum. This was then dissolved in DCM (200 mL), washed with water (200 mL) and brine (200 mL). The organic layer was passed through phase separating cartridge and concentrated under reduced pressure. The crude material was suspended in DCM, solid filtered off and dried to give EN01580-46-2 N-(4-chloropyridin-2-yl)pyrimidin-2-amine (2.975 g, 42.6 %). The filtrate was purified by silica gel chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford EN01580-46-1, N-(4-chloropyridin-2-yl)pyrimidin-2-amine (0.889 g, 12.73 %) as a white solid. |
Here is a chemical reaction formula: Reactants are:amine:CC1=C(C=C(C=C1)N)NC(=O)C;aryl halide:CN1C=C(N=C1)NC2=CC(=NC3=C(C=NN23)C#N)Cl, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC(=O)N(C)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], and Products are 0:CC1=C(C=C(C=C1)NC2=NC3=C(C=NN3C(=C2)NC4=CN(C=N4)C)C#N)NC(=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a microwave vial containing N-(5-amino-2-methylphenyl)acetamide (0.096 g, 0.58 mmol), 5-chloro-7-(1-methyl-1H-imidazol-4-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.08 g, 0.29 mmol), sodium tert-butoxide (0.093 g, 0.96 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.014 g, 0.03 mmol) was added DMA (1.8 ml). Vial was flushed with argon and to it was added Pd2(dba)3 (0.013 g, 0.01 mmol) and the reaction was heated in a MW reactor at 100 C for 50 min . Reaction was filtered through celite and the filterate diluted with EtOAC (5 ml) and the organic solution was washed with minimum amt of brine( 1X 5 ml) and organic layer dried over Na2SO4 filtered and concentrated to give crude liquid. this was purified by flash column using 5-8% MeOH: DCM (1% NH4OH) as gradient to give N-(5-(3-cyano-7-(1-methyl-1H-imidazol-4-ylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-methylphenyl)acetamide (0.015 g, 12.78 %) as desired product. nmr & MASS AGREE WITH THE STRUCTURE. |
Here is a chemical reaction formula: Reactants are:amine:CC1=C(C=C(C=C1)N)NC(=O)C;aryl halide:CN1C=C(N=C1)NC2=CC(=NC3=C(C=NN23)C#N)Cl, 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:CC(=O)N(C)C;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=C(C=C(C=C1)NC2=NC3=C(C=NN3C(=C2)NC4=CN(C=N4)C)C#N)NC(=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a microwave vial containingN-(5-amino-2-methylphenyl)acetamide (0.120 g, 0.73 mmol), 5-chloro-7-(1-methyl-1H-imidazol-4-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.1 g, 0.37 mmol) ,sodium 2-methylpropan-2-olate (0.116 g, 1.21 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.017 g, 0.04 mmol)was added DMA (2.2 ml). Vial was flushed with argon and to it was added Pd2(dba)3 (0.017 g, 0.02 mmol) and the reaction was heated in a MW reactor at 100 ° C for 60 min.Reaction was filtered, and filterate concentrated under reduced pressure to give dark red gum. This was suspended in 10% MeOH : DCM (10 ml) filtered and filterate concentrated to give crude solid. This was purified by flash column using 5-8% MeoH :DCM (1% NH4OH) to give 75 mg of pale yellow solid (EN02331-12-1). LCMS short purity indicated 90% pure. This sample was further purified by triturating the solid in 20% EtOAC: ether (10ml). The solid was filtered, dried to give pale yellow solid (EN 02331-12-2) as desired pdt. Mass spec and NMR are in agreement with the structure. (Note : The Etoac:Ether solution(filterate in the above step) obtained after trituration was concentrated to give solid (23 mg) this was stored for future use. |
Here is a chemical reaction formula: Reactants are:amine:CC(=O)NC1=C(C=CC(=C1)N)N(C)CCO;aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl, 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:CC(=O)N(C)C, and Products are 0:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)N(C)CCO, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (120mg, 0.51 mmol), N-(5-amino-2-((2-hydroxyethyl)(methyl)amino)phenyl)acetamide (115 mg, 0.51 mmol), and cesium carbonate (335 mg, 1.03 mmol) in DMA (3.0 mL) (),Pd2(dba)3 (23.51 mg, 0.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (29.7 mg, 0.05 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed SM and product. under microwave 150C for another 2h. 15% SM remained. MeOH (2 mL) was added to the reaction mixture. filtered. The mother liquid solvent was removed by ratovapor to yield stick oil. The crude product was loaded on ISCO (Hex to Hex:EtOAc To EtOAc to EtOAc:MeOH=10:1) to give sticky oil. The product was not pure. added 1 mL of EtOAc, the solid was promoted to form by scratching the flask wall. The resulting suspension was heated to reflux. When it was warm, the mixture was filtered to give offwhite solid. This solid was washed with EtOAc ( 2 mL) and dried at 80C under reduced press oven to give N-(5-(3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-((2-hydroxyethyl)(methyl)amino)phenyl)acetamide (110 mg, 50.9 %) NMR and LCMS showed desired product, see attachment |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CN=C1)Br;amine:C1CC(C1)N2CCN(CC2)C(=O)C3CC4(C3)CCNCC4, 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:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CC(C1)N2CCN(CC2)C(=O)C3CC4(C3)CCN(CC4)C5=CN=CC=C5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: cesium carbonate (123 mg, 0.38 mmol) was added to a solution of (4-cyclobutylpiperazin-1-yl)(7-azaspiro[3.5]nonan-2-yl)methanone (100 mg, 0.34 mmol), PdOAc2 (7.70 mg, 0.03 mmol), BINAP (42.7 mg, 0.07 mmol) and 3-bromopyridine (56.9 mg, 0.36 mmol) in toluene (2 mL). The reaction mixture was heated to 110°C for 18hrs. The room temperature cooled down mixture was filtered over celite. The solvent was concentrated. The product was purified by preparative HPLC using a low pH shallow gradient method (Mobile phase: 20-40% B; A: H2O with 0.05% TFA , B: CH3CN, 25 min. run) on Luna 15 m, C8 (2), 21.2x250 mm Phenomenex reverse phase column to provide (4-cyclobutylpiperazin-1-yl)(7-(pyridin-3-yl)-7-azaspiro[3.5]nonan-2-yl)methanone (10.00 mg, 7.91 %) as white solid. 1H NMR (400 MHz, CHLOROFORM- _d_ ) d ppm 1.58 (s, 3 H) 1.63 (dd, _J_ =6.25, 4.69 Hz, 2 H) 1.66 - 1.79 (m, 3 H) 1.80 - 1.94 (m, 2 H) 1.97 - 2.10 (m, 3 H) 2.12 - 2.21 (m, 2 H) 2.27 (q, _J_ =5.60 Hz, 3 H) 2.71 (quin, _J_ =7.91 Hz, 1 H) 3.21 (quin, _J_ =8.79 Hz, 1 H) 3.32 - 3.39 (m, 2 H) 3.41 (dd, _J_ =6.64, 4.69 Hz, 2 H) 3.54 (dd, _J_ =6.25, 4.69 Hz, 2 H) 3.63 (t, _J_ =4.88 Hz, 2 H) 6.53 - 6.60 (m, 1 H) 6.65 (d, _J_ =8.59 Hz, 1 H) 7.40 - 7.48 (m, 1 H) 8.16 (td, _J_ =2.34, 1.17 Hz, 1 H) HRMS _m/z_ calcd for C22H32N4O 369.26489 [M+H]+, found 369.26533. MS _m/z_ 369.2 [M+H]\+ (ES+) |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C=C1)Br)OC;amine:CC(C)[C@@H]1CNCCN1C(=O)OC(C)(C)C, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;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@@H]1CN(CCN1C(=O)OC(C)(C)C)C2=CC(=C(C=C2)OC)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 21-Apr-09 08:58:54 +0100 4-bromo-1,2-dimethoxybenzene (0.068 mL, 0.46 mmol), (R)-tert-butyl 2-isopropylpiperazine-1-carboxylate (126 mg, 0.55 mmol) and 2-Dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (11.21 mg, 0.03 mmol) and Sodium tert-butoxide (63.9 mg, 0.64 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (21.09 mg, 0.02 mmol) were suspended in toluene (5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 20 minutes in the microwave reactor and cooled to RT. LC-MS shows 36% product and 57% SM reaction will be combined with EN02263-47 |
Here is a chemical reaction formula: Reactants are:amine:CC(C)[C@@H]1CNCCN1C(=O)OC(C)(C)C;aryl halide:COC1=C(C=C(C=C1)Br)OC, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;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@@H]1CN(CCN1C(=O)OC(C)(C)C)C2=CC(=C(C=C2)OC)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 21-Apr-09 08:58:54 +0100 4-bromo-1,2-dimethoxybenzene (0.135 mL, 0.92 mmol), (R)-tert-butyl 2-isopropylpiperazine-1-carboxylate (252 mg, 1.11 mmol) and 2-Dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (10.88 mg, 0.03 mmol) and Sodium tert-butoxide (128 mg, 1.29 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (21.09 mg, 0.02 mmol) were suspended in toluene (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. LC-MS show sproduct at 60% and SM 33% reaction mixture to be combined with EN02263-45 and worked up. |
Here is a chemical reaction formula: Reactants are:amine:CC(C)[C@@H]1CNCCN1C(=O)OC(C)(C)C;aryl halide:COC1=C(C=C(C=C1)Br)OC, Reagents are:Base:CC(C)(C)[O-].[K+];metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Pd];Solvent:C1CCOC1, and Products are 0:CC(C)[C@@H]1CN(CCN1C(=O)OC(C)(C)C)C2=CC(=C(C=C2)OC)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 22-Apr-09 09:56:23 +0100 4-bromo-1,2-dimethoxybenzene (0.068 mL, 0.46 mmol), (R)-tert-butyl 2-isopropylpiperazine-1-carboxylate (126 mg, 0.55 mmol) and BIS(TRI-T- BUTYLPHOSPHINE)PALLADIUM(0) (23.54 mg, 0.05 mmol) and potassium 2-methylpropan-2-olate (76 mg, 0.64 mmol) were suspended in THF (5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. LC-MS shows no starting material. The reaction mixture was filtered and the crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(3,4-dimethoxyphenyl)-2-isopropylpiperazine-1-carboxylate (152 mg, 91 %) as a yellow gum. |
Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N;aryl halide:CC1=C(C=CC(=N1)Cl)F, Reagents are:Base:[O-]P(=O)([O-])[O-].[K+].[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: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, and Products are 0:CC1=C(C=CC(=N1)NC(=O)OC(C)(C)C)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 6-chloro-3-fluoro-2-methylpyridine (500 mg, 3.43 mmol), tert- Butyl carbamate (523 mg, 4.47 mmol), Potassium phosphate (1094 mg, 5.15 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (99 mg, 0.17 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (79 mg, 0.09 mmol) were combined in a sealed vial which was purged with nitrogen. Degassed toluene (5 mL) and water (5.00 mL) were added and the mixture was stirred under a nitrogen atmosphere at 90 °C for 6h. The reaction mixture was diluted with EtOAc and washed with saturated NaHCO3 solution, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with mixtures of 5-50%EtOAc in heptane. Many spots isolated, but none of them seemed to be the desired product. Not continued. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=CC(=CC(=C1)Br)[N+](=O)[O-];amine:CN1CCNCC1, 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:CN1CCN(CC1)C2=CC(=CC(=C2)C(=O)OC)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: To the stirred suspension ofmethyl 3-bromo-5-nitrobenzoate (2 g, 7.69 mmol) , cesium carbonate (12.53 g, 38.46 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.111 g, 0.19 mmol) in Dioxane (12 mL) (degassed with N2) was added pd (dba)3 (0.176 g, 0.19 mmol) and cesium carbonate (12.53 g, 38.46 mmol) AND rxn was heated at 110 ºC for 1 hr in microwaved. LCMS showed the m+1= 280. The crude raection mixture was filtered over celite. The filtrate was concentarted. The crude solid was diluted by 20 mL ethyl acetate, washed with 3x10 mL water, brine, collected the organic layers, concentrated. The crude solid was added to a silica gel column and was eluted with 0-10% methanol in DCM. Collected desired fractions. Obtained=1.4 gm. 1H NMR (300 MHz, DICHLOROMETHANE- _d_ 2) d ppm 2.32 (s, 3 H) 2.43 - 2.64 (m, 4 H) 3.13 - 3.40 (m, 4 H) 3.93 (s, 3 H) 7.85 (d, _J_ =1.70 Hz, 2H) 8.18 (t, _J_ =1.60 Hz, 1 H) Registered as AZ13477915. |
Here is a chemical reaction formula: Reactants are:amine:C1CNCCN1;aryl halide:CC1=C(C=C(C=C1)Br)[N+](=O)[O-], Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];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:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=C(C=C(C=C1)N2CCNCC2)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: palladium(II) acetate (0.065 g, 0.29 mmol), BINAP (0.144 g, 0.23 mmol) and CS2CO3 (0.943 g, 2.89 mmol) were added to a mixture of 4-bromo-1-methyl-2-nitrobenzene (0.5 g, 2.31 mmol) and piperazine (1.623 g, 18.84 mmol) . The suspension were heated to 110 °C for 24 hours, LCMS showed product mass [M+1]: 222.1 at retension time RT=1.21 min (polar short purity method). Workup reaction by additional of water (10mL), extracted with EtOAc (3x20 mL), washed with brine, dried with Na2SO4, evaporated off solvent to give a residue, which was purified by isco chromatographer, eluting with 0-10% MeOH in DCM to give 1-(4-methyl-3-nitrophenyl)piperazine (0.201 g, 39.3 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=C(C=C1)Br)[N+](=O)[O-];amine:C1CNCCN1, 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:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=C(C=C(C=C1)N2CCNCC2)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: palladium(II) acetate (0.390 g, 1.74 mmol), BINAP (0.865 g, 1.39 mmol) and CS2CO3 (5.66 g, 17.36 mmol) were added to a mixture of 4-bromo-1-methyl-2-nitrobenzene (3 g, 13.89 mmol) and piperazine (9.74 g, 113.04 mmol) in microwave. The suspension were heated to 110 °C for 24 hours, LCMS showed product mass [M+1]: 222.0 at retension time RT=1.38 min (polar short purity method). Workup reaction by additional of water (10mL), extracted with EtOAc (3x20 mL), washed with brine, dried with Na2SO4, evaporated off solvent to give a residue, which was purified by isco chromatographer, eluting with 0-10% MeOH in DCM to give 1-(4-methyl-3-nitrophenyl)piperazine (1.670 g, 54.4 %) as a yellow solid. LCMS confirmed the target compound. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1CC(C1)NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC1=CC(=C(C=C1NC(=O)C)N)F, 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: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=CC(=C(C=C1NC(=O)C)NC2=NC3=C(C=NN3C(=C2)NC4CCC4)C#N)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-chloro-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.32 mmol), N-(5-amino-4-fluoro-2-methylphenyl)acetamide (58.8 mg, 0.32 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (18.69 mg, 0.03 mmol) in DMA (5 mL) were added to a microwave tube. Pd2(dba)3 (14.79 mg, 0.02 mmol) and cesium carbonate (210 mg, 0.65 mmol) were added. The solution was degassed, filled with N2, capped, then microwaved at 150C for 30 min. The organic solvent was removed. TLC showed two closely associated peaks, so product was purified via Gilson. Appropriate fractions were collected, concentrated by rotovap, and dried in the oven overnight. LCMS, HPLC, and NMR revealed desired product. See attachments. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(N=CC(=N1)Cl)C(F)(F)F;amine:CC(C)(C)OC(=O)N1CCNCC1, 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:CC(C)(C)[O-].[Na+], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=NC=C(N=C2)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 20 mL microwave vial was charged with 2-chloro-5-(trifluoromethyl)pyrazine (1 g, 5.48 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.341 g, 0.55 mmol), Sodium tert-butoxide (0.632 g, 6.57 mmol), tert-butyl piperazine-1-carboxylate (1.020 g, 5.48 mmol) and a mixture of toluene (25 mL) and DMF (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0) (0.251 g, 0.27 mmol) was added. The reaction mixture was stirred at 105°C in an oil bath 12h. The solution was diluted with EtOAc and washed with saturated NaHCO3 solution, brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was loaded on a 80g silica gel column and purified on a Teledyne Isco instrument, eluting with 0% to 25% ethyl acetate in heptane to provide tert-butyl 4-(5-(trifluoromethyl)pyrazin-2-yl)piperazine-1-carboxylate (0.390 g, 21.41 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C2C(=C1)C=CC(=N2)Cl;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=NC3=CC=CC=C3C=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 2.0-5.0 mL microwave vial was charged with tert-Butyl 1-piperazinecarboxylate (100 mg, 0.54 mmol), 2-Chloroquinoline (0.086 mL, 0.64 mmol), Sodium tert-butoxide (61.9 mg, 0.64 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (33.4 mg, 0.05 mmol) and toluene (3 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0) (24.58 mg, 0.03 mmol) was added. The reaction mixture was stirred at 100°C in an oil bath for 12h. The solution was diluted with EtOAc and washed with saturated NaHCO3, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was loaded on a 40g silica gel column and purified on a Teledyne Isco instrument, eluting with 10% to 40% ethyl acetate in heptane. Product not pure. Product was repurifed using a 40g Gold column with same eluent to provide tert-butyl 4-(quinolin-2-yl)piperazine-1-carboxylate (78 mg, 46.4 %) as a solid. MS m/z 314.3 [M+H]+ (ESI) |
Here is a chemical reaction formula: Reactants are:amine:CC1=CN=C(C=C1NC(=O)C)N;aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)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+];Solvent:CN(C)C=O, and Products are 0:CC1=CN=C(C=C1NC(=O)C)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Ref: _Angew. Chem. Int. Ed._ **2006** , _45_ , 6523-6527 1\. To a microwave tube was added N-(2-amino-5-methylpyridin-4-yl)acetamide (43 mg, 0.26 mmol), 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (85 mg, 0.36 mmol), Cs2CO3 (254 mg, 0.78 mmol), Pd2dba3 (23.84 mg, 0.03 mmol), and di- tert-butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (22.11 mg, 0.05 mmol). The mixture was dissolved in DMF (1 mL) and sealed. The tube was de-gassed and inflated with N2. 2\. The reaction was heated at 90°C in oil-bath for 4 hr. LCMS showed partial formation of product. Heated overnight at 90°C. 3\. The reaction mixture was filtered through celite pad and the filtrate was loaded onto column and run chromotography to purify (10% MeOH in DCM), semi- pure product was obtained and the sample was submitted to analytical group for further purification. 4\. 10 mg pure product was obtained. 1H NMR (400 MHz, DMSO- _d_ 6) d ppm 0.73 (d, _J_ =2.78 Hz, 2 H) 0.85 (d, _J_ =5.05 Hz, 2 H) 2.15 (d, _J_ =12.88 Hz, 7 H) 2.62 (br. s., 1 H) 7.36 (s, 1 H)7.98 (s, 1 H) 8.09 (s, 1 H) 8.35 (s, 1 H) 8.38 (s, 1 H) 9.38 (s, 1 H) 10.11 (s, 1 H) |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC(=C1)Br)C(F)(F)F;amine:C1CNCCC1O, 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:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:C1CN(CCC1O)C2=CC=CC(=C2)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 1-bromo-3-(trifluoromethyl)benzene (6.13 mL, 44.44 mmol), piperidin-4-ol (5.608 g, 55.44 mmol), diacetoxypalladium (0.200 g, 0.89 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.553 g, 0.89 mmol) and cesium carbonate (18.10 g, 55.55 mmol) in dioxane (100 mL) was evacuated and backfilled with N2 three times and then it was heated at 100 °C for 6h. The mixture was filtered through filter agent(supercell), washed with EtOAc. The combined filtrate was concentrated. The residue was purified by silica gel column(0-35% EtOAc/hexane) to give 1-(3-(trifluoromethyl)phenyl)piperidin-4-ol (4.70 g, 43.1 %) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) d 7.38 (t, _J_ = 8.03 Hz, 1H), 7.20 (dd, _J_ = 2.38, 8.41 Hz, 1H), 7.13 (s, 1H), 7.00 (d, _J_ = 7.78 Hz, 1H), 4.64 - 4.72 (m, 1H), 3.53 - 3.72 (m, 3H), 2.93 (ddd, _J_ = 3.01, 9.98, 12.86 Hz, 2H), 1.71 - 1.88 (m, 2H), 1.45 (dtd, _J_ = 3.89, 9.44, 12.86 Hz, 2H). LCMS 246. |
Here is a chemical reaction formula: Reactants are:amine:C1COCCC1N;aryl halide:C1=CC(=NC(=C1)Br)Br, 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:C1COCCC1NC2=NC(=CC=C2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: to 2,6-dibromopyridine (100 mg, 0.42 mmol), 4-Aminotetrahydropyran (42.7 mg, 0.42 mmol) in dioxane (3 mL) while bubbling N2 was added Xantphos (24.43 mg, 0.04 mmol), CS2CO3 (316 mg, 0.97 mmol) and palladium(II) acetate (9.48 mg, 0.04 mmol). This was heated in a microwave at 130 oC for 30 mins. A small peak corresponding to product was obseved. Discontinued |
Here is a chemical reaction formula: Reactants are:aryl halide:C1C(CO1)NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC1=C(C=C(C=C1)N)NC(=O)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC(=O)N(C)C;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)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:CC1=C(C=C(C=C1)NC2=NC3=C(C=NN3C(=C2)NC4COC4)C#N)NC(=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a microwave tube, was Cs2CO3 (0.522 g, 1.60 mmol), N-(5-amino-2-methylphenyl)acetamide (0.132 g, 0.80 mmol), Pd2dba3 (0.037 g, 0.04 mmol),5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.200 g, 0.80 mmol),di-tert- butyl(2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphine (0.034 g, 0.08 mmol). anhydrous DMA (2.0 mL) was added. The resulting mixture was bubbled through N2. Then the tube was capped. under microwave 145C for 30min. This reaction was repeated at 150mg again. The two batches were combined to workup The mixture was concentrated to dryness. Water (20 mL) was added. it was extracted with 10% MeOH in EtOAc, The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness. It was purified by chromatography )Hex to 50% etAOc in Hex to EtOAc to 5% MeOH in EtOAc) to collect the pure product to give the product (86mg, 16.5% from total 350mg SM 5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile) which was washed with EtOAc and dried under a high vacuum at 60C for 16h as an offwhite solid |
Here is a chemical reaction formula: Reactants are:amine:COC1=NC(=NC=C1Br)N;aryl halide:C1=CC(=C(C=C1C(F)(F)F)I)F, 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:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC1=NC(=NC=C1Br)NC2=C(C=CC(=C2)C(F)(F)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a microwave vial was added a mixture of 5-bromo-4-methoxypyrimidin-2-amine (0.520 g, 2.55 mmol), diacetoxypalladium (0.059 g, 0.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (151.8 mg, 0.26 mmol), 1-fluoro-2-iodo-4-(trifluoromethyl)benzene (0.89 g, 3.07 mmol) and toluene (17 mL) under inert atmosphare. The reaction mixture was sealed and heated at 90 °C under 16h. The LCMS indicated a complete conversion of the SM. The reaction mixture was partitioned between ethyl acetate and NH4Cl-solution. The organic layer was washed with NH4Cl-solution, brine dried over sodium sulphate, filtered and concentrated in vacuum to give a yellow gum. The oil dissolved in dichloromethane charged on silica 100g and purified by flash chromatography eluting with Ethyl acetate (0-80)% in heptane giving the product 5-bromo-N-(2-fluoro-5-(trifluoromethyl)phenyl)-4-methoxypyrimidin-2-amine (792 mg, 85 %) as a white solid. Collected at 260 nm 1H NMR (500 MHz, DMSO) d 3.93 (s, 3H), 7.49 (td, 2H), 8.29 - 8.35 (m, 1H), 8.40 (s, 1H), 9.60 (s, 1H). Expected Number of Hs: 8 Assigned Hs: 8. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1C(F)(F)F)I)F;amine:COC1=NC(=NC=C1Br)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:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC1=NC(=NC=C1Br)NC2=C(C=CC(=C2)C(F)(F)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a microwave vial was added a mixture of 5-bromo-4-methoxypyrimidin-2-amine (0.570 g, 2.79 mmol), diacetoxypalladium (0.059 g, 0.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152.9 mg, 0.26 mmol), 1-fluoro-2-iodo-4-(trifluoromethyl)benzene (0.99 g, 3.41 mmol) and toluene (17 mL) under inert atmosphare. The reaction mixture was sealed and heated at 100 °C under 16h. The LCMS indicated a complete conversion of the SM. The reaction mixture was partitioned between ethyl acetate and aqueous NH4Cl- solution. The organic layer was washed with NH4Cl-solution, brine dried over sodium sulphate, filtered and concentrated in vacuum to give a yellow gum. The oil dissolved in dichloromethane charged on silica 100g and purified by flash chromatography eluting with Ethyl acetate (0-80)% in heptane giving the product 5-bromo-N-(2-fluoro-5-(trifluoromethyl)phenyl)-4-methoxypyrimidin-2-amine (827 mg, 81 %) as a white solid. Collected at 260 nm 1H NMR (500 MHz, DMSO) d 3.94 (d, 3H), 7.45 - 7.53 (m, 2H), 8.33 (t, 1H), 8.40 (d, 1H), 9.60 (s, 1H). Expected Number of Hs: 8 Assigned Hs: 8. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=NC(=C1)Br;amine:C1CC(C1)N2CCN(CC2)C(=O)C3CC34CCNCC4, Reagents are:Solvent:CC1=CC=CC=C1;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:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:C1CC(C1)N2CCN(CC2)C(=O)C3CC34CCN(CC4)C5=CC=CC=N5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (4-cyclobutylpiperazin-1-yl)(6-azaspiro[2.5]octan-1-yl)methanone (100 mg, 0.36 mmol), Sodium tert-butoxide (34.6 mg, 0.36 mmol) and 2-bromopyridine (62.7 mg, 0.40 mmol) were weighted in a microwave vial. A solution of Palladium(II) acetate (4.05 mg, 0.02 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (X-Phos) (8.59 mg, 0.02 mmol) in toluene (3.75 mL) and tert-butanol (0.75 mL)was added and the mixture heated at 160 °C for 10 minutes, and then 20 minutes more. The mixture was evaporated to dryness, redissolved in a minimum of methanol, filtered and purified on preparative HPLC using the long high pH (acetonitrile in water ammonium carbonate buffer, 25 min.) 20 to 40% gradient method on XBridge Prep C18 OBD, 30x150 mm, 5 mm, Waters reverse phase column, giving (4-cyclobutylpiperazin-1-yl)(6-(pyridin-2-yl)-6-azaspiro[2.5]octan-1-yl)methanone (34.0 mg, 26.6 %) as a slightly yellow solid after lyophilization. 1H NMR (400 MHz, DMSO- _d_ 6) d ppm 0.75 (dd, _J_ =7.81, 3.91 Hz, 1 H) 1.06 (t, _J_ =4.49 Hz, 1 H) 1.31 - 1.67 (m, 6 H) 1.74 (d, _J_ =10.16 Hz, 2 H) 1.85 - 2.00 (m, 3 H) 2.01 - 2.36 (m, 4 H) 2.65 (quin, _J_ =7.52 Hz, 1 H) 3.35 - 3.69 (m, 8 H) 6.58 (dd, _J_ =6.64, 5.08 Hz, 1 H) 6.82 (d, _J_ =8.59 Hz, 1 H) 7.49 (td, _J_ =7.81, 1.95 Hz, 1 H) 8.08 (dd, _J_ =4.88, 1.37 Hz, 1 H) HRMS _m_ / _z_ calcd for C21H31N4O [M + H]+ 355.24924, found 355.24965. |
Here is a chemical reaction formula: Reactants are:amine:C1CC(C1)N2CCN(CC2)C(=O)C3CC34CCNCC4;aryl halide:C1=CC=NC(=C1)Br, Reagents are:Base:CC(C)(C)[O-].[Na+];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:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1CC(C1)N2CCN(CC2)C(=O)C3CC34CCN(CC4)C5=CC=CC=N5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Reagents were put in a sealed vial and heated in the microwave oven for 10 minutes at 160°C. According to LC-MS analysis, the conversion is >90%. The crude mixture was transferred to a round-bottomed flask and volatiles were evaporated under vacuum. The residue was purified on preparative HPLC using the long high pH (acetonitrile in water ammonium carbonate buffer, 25 min.) 20 to 40% gradient method on XBridge Prep C18 OBD, 30x150 mm, 5 mm, Waters reverse phase column, giving (4-cyclobutylpiperazin-1-yl)(6-(pyridin-2-yl)-6-azaspiro[2.5]octan-1-yl)methanone (7.20 mg, 9.39 %). However, the compound was not pure enought for submission and there was not enough of it to attempt another purification. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:C1=CC(=CC2=C1C=CN2)CO, 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: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:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)N4C=CC5=C4C=C(C=C5)CO, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (50 mg, 0.21 mmol), [Reactants], and cesium carbonate (77 mg, 0.24 mmol) in DMA (0.5 mL) ([VOLUME]),Pd2(dba)3 (9.80 mg, 10.70 µmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (12.38 mg, 0.02 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed completion. added MeOH (3 mL), filtered through celite. concentrated. The residue was purified by ISCO (Hexane to EtOAc:Hex=1;1 to EtOAc) to give about 34 mg offwhite solid |
Here is a chemical reaction formula: Reactants are:amine:CC(=O)NC1=C(C=CC(=C1)N)N2CCN(CC2)C;aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)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: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(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)N5CCN(CC5)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.34 mmol), [Reactants], and cesium carbonate (145 mg, 0.45 mmol) in DMA (0.5 mL) ([VOLUME]),Pd2(dba)3 (15.68 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (19.81 mg, 0.03 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed completion. concentrated. loaded on ISCO (Hex to Hex:EtOAc To EtOAc:MeOH=10:1 to EtOAc:MeOH:Et3N=10:1:0.1) to give yellow solid. This yellow solid was washed with EtOAc(1mL) to give 40mg pure compound. NMR, 1H,HPLC are OK, see attachment |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=C(C=C(C=C1)Br)Cl;amine:CC(C)(C)OC(=O)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:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC(=C(C=C2)C(=O)OC)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of palladium acetate (18.00 mg, 0.08 mmol) in dry toluene (16 mL) under nitrogen was added BINAP (100 mg, 0.16 mmol). The reaction was heated to 80 °C and stirred for 10 min. To the reaction was then added tert- butyl piperazine-1-carboxylate (299 mg, 1.60 mmol), cesium carbonate (261 mg, 0.80 mmol), potassium carbonate (222 mg, 1.60 mmol), 18-crown-6 (42.4 mg, 0.16 mmol) and methyl 4-bromo-2-chlorobenzoate (400 mg, 1.60 mmol). The reaction was stirred at 80°C overnight, filtered through celite and washed with small amounts of DCM. The filtrate was concentrated under reduced pressure and purified by flash chromatography on silica gel, eluting with mixtures of EtOAc and heptane, to afford tert-butyl 4-(3-chloro-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate (517 mg, 91 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1C(CO1)NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC(=O)NC1=C(C=CC(=C1)N)C2CC2, 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(C(C)(C)C)C(C)(C)C)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:CC(=O)N(C)C, and Products are 0:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4COC4)C#N)C5CC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 10 mL microwave reactor vial was charged with 5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.32 mmol), N-(5-amino-2-cyclopropylphenyl)acetamide (67.1 mg, 0.35 mmol), Cs2CO3 (313 mg, 0.96 mmol), Pd2(dba)3 (14.67 mg, 0.02 mmol) and 2-Di-t- butylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (13.61 mg, 0.03 mmol). The suspended in DMA (.5 mL), added via syringe. The resulting brown suspension was stirred under nitrogen, then microwave vial capped and heated at 150 °C under microwave irradiation for 20 min. LCMS indicated formation of product. The cooled reaction mixture was put through vacuum filtration and concentrated in rotovap. The crude material was purified by ISCO using MeOH and EtOAc (1:10). The solid was suspended in water, stirred for 12 h at rt, repurified with EtOAc, collected and dried to afford a light brown powder (9 mg, 6%) at 93% purity. LCMS, HPLC, and HNMR consistent with desired product- see attached. |
Here is a chemical reaction formula: Reactants are:amine:CC(=O)NC1=C(C=CC(=C1)N)C2CC2;aryl halide:C1C(CO1)NC2=CC(=NC3=C(C=NN23)C#N)Cl, Reagents are:Solvent:CN(C)C=O;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)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:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4COC4)C#N)C5CC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Ref: _Angew. Chem. Int. Ed._ **2006** , _45_ , 6523-6527 1\. To a microwave tube was added N-(5-amino-2-cyclopropylphenyl)acetamide (0.038 g, 0.20 mmol), 5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.060 g, 0.24 mmol), Cs2CO3 (0.196 g, 0.60 mmol), Pd2dba3 (0.018 g, 0.02 mmol), and di-tert-butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.017 g, 0.04 mmol). The mixture was dissolved in DMF (0.5 mL) and sealed. The tube was de- gassed and inflated with N2. 2\. The reaction was heated at 90°C in oil-bath overnight. LCMS showed SM and byproducts and small amount of product mass. did not workup |
Here is a chemical reaction formula: Reactants are:aryl halide:C1C(CO1)NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC(=O)NC1=C(C=CC(=C1)N)C2CC2, Reagents are:Solvent:CC(=O)N(C)C;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)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:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4COC4)C#N)C5CC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a microwave tube, was Cs2CO3 (0.522 g, 1.60 mmol), N-(5-amino-2-cyclopropylphenyl)acetamide (0.152 g, 0.80 mmol), Pd2dba3 (0.037 g, 0.04 mmol),5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.200 g, 0.80 mmol),di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.034 g, 0.08 mmol). anhydrous DMA (1.0 mL) was added. The resulting mixture was bubbled through N2. Then the tube was capped. under microwave 145C for 25min. LCMS showed product and byproduct mass, did not showed SM The mixture was filtered through celite. The resulting black solution was concentrated to dryness by rotavapor. The crude product was purified by ISCO (40g, Hex to EtOAc:HEx=1;2 to 1;1 to EtOAcO) to give product (offwhite solid). HPLC showed some impurity. This offwhite solid was washed with warm EtOAc (1mL) to give N-(5-(3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-cyclopropylphenyl)acetamide (0.028 g, 8.66 %). LCMS and NMR were OK< see attachment. |
Here is a chemical reaction formula: Reactants are:amine:CC(=O)NC1=C(C=CC(=C1)N)N2CCC[C@H](C2)N(C)C;aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl, 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:CC(=O)N(C)C, and Products are 0:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)N5CCC[C@H](C5)N(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (120mg, 0.51 mmol), (R)-N-(5-amino-2-(3-(dimethylamino)piperidin-1-yl)phenyl)acetamide (142 mg, 0.51 mmol), and cesium carbonate (335 mg, 1.03 mmol) in DMA (0.5 mL) (),Pd2(dba)3 (23.51 mg, 0.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (29.7 mg, 0.05 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed completion. added MeOH (2 mL), filtered. The solvent was removed by ratovapor to yield stick oil. The crude product was loaded on ISCO (Hex to Hex:EtOAc To EtOAc to EtOAc:MeOH:Et3N=10:1:0.1) to give sticky oil. The product was not pure. It was purifed by to give (R)-N-(5-(3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-(3-(dimethylamino)piperidin-1-yl)phenyl)acetamide (22.00 mg, 7.29 %) as a light brown solid (TFA salt). the solid was dried under high vacuum under 60C for 2h. LCMS and NMR were OK, see the attachment |
Here is a chemical reaction formula: Reactants are:amine:CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)N;aryl halide:C1=C(C=C(C(=C1F)F)Br)F, 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: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(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)NC4=C(C(=CC(=C4)F)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (350 mg, 1.01 mmol), cesium carbonate (1288 mg, 3.95 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (147 mg, 0.25 mmol) and 1-bromo-2,3,5-trifluorobenzene (470 mg, 2.23 mmol) in degassed 1,4-dioxane (2.2ml), was added TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (69.6 mg, 0.08 mmol). The suspension was heated in a sealed container up to 85-95°C for 24 hours. The reaction mixture was filtered through a short pad of dicalite, concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford the N,N-dimethyl-2-morpholino-4-oxo-8-(1-(2,3,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide (400 mg, 83 %) as a yellow gum, which still containing some impurities. The product mixture was then re-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,N-dimethyl-2-morpholino-4-oxo-8-(1-(2,3,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide (135 mg, 28 %) as a clear yellow solid. |
Here is a chemical reaction formula: Reactants are:amine:CC1=C(C=C(C=C1)N)NC(=O)C;aryl halide:CN1C=CC(=N1)NC2=CC(=NC3=C(C=NN23)C#N)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: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=C(C=C1)NC2=NC3=C(C=NN3C(=C2)NC4=NN(C=C4)C)C#N)NC(=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: in microwave tube was 5-chloro-7-(1-methyl-1H-pyrazol-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.29 mmol), N-(5-amino-2-methylphenyl)acetamide (48.0 mg, 0.29 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (16.91 mg, 0.03 mmol) in DMA (0.5 mL).Pd2(dba)3 (13.38 mg, 0.01 mmol) and cesium carbonate (105 mg, 0.32 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. added 2 mL of MeOH, filtered through celite. concentrated. The residue was purified by ISCO (Hex to Hex:EtOAc=1:4 to 1:1 to EtOAc), collected prod fractions. concentrated to give offwhite solid. This solid was washed with 0.5 mL of EtOAc to give pure prod |
Here is a chemical reaction formula: Reactants are:amine:CC1=CC(=C(C=C1NC(=O)C)N)F;aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl, 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:CC(=O)N(C)C, and Products are 0:CC1=CC(=C(C=C1NC(=O)C)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: in microwave tube was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.34 mmol), N-(5-amino-4-fluoro-2-methylphenyl)acetamide (62.4 mg, 0.34 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (19.81 mg, 0.03 mmol) in DMA (0.5 mL).Pd2(dba)3 (15.68 mg, 0.02 mmol) and cesium carbonate (223 mg, 0.68 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. the organic solvent was removed. The black residue was tried to purifed by ISCO. impurity and prod came out together too quickly. concentrated to give offwhite solid. LCMS showed about 10% impurity. The solid was washed with hot EtOAc(1mL) to give about 21mg white solid. LCMS and NMR are OK, see attachment. low yield was due to hot EtOAc wash, lost some prod. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1Br)F)C(F)(F)F;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:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC(=C(C=C2)C(F)(F)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask, PALLADIUM ACETATE (0.014 g, 0.06 mmol) was treated with BINAP (0.077 g, 0.12 mmol) under nitrogen in degassed Toluene (12.35 ml). The reaction was heated to 80 °C and was stirred for 10 min. To the flask was then added tert-butyl piperazine-1-carboxylate (0.230 g, 1.23 mmol), cesium carbonate (0.201 g, 0.62 mmol), potassium carbonate (0.171 g, 1.23 mmol), and 18-CROWN-6 (0.033 g, 0.12 mmol). The reaction was then treated with 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (0.300 g, 1.23 mmol) and was allowed to stir at 80°C 5 h. **LCMS High pH:** SM Amine Rt = 1.21 min Product Rt = 2.14 min, Rf = 0.28 The reaction mixture was filtered through celite and washed with small amounts of DCM. The filtrate was evaporated in vacuo to a residue that was taken up in a mixture of Heptane and EtOAc (4:1). The residue was purified by flash chromatography on silica gel, eluting with mixtures of EtOAc and heptane, to afford tert-butyl 4-(3-fluoro-4-(trifluoromethyl)phenyl)piperazine-1-carboxylate (0.258 g, 59.9 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1Cl)Br)F;amine:CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)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: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:CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)NC4=CC(=CC(=C4)Cl)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (350 mg, 1.01 mmol), cesium carbonate (1288 mg, 3.95 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (147 mg, 0.25 mmol) and 1-bromo-3-chloro-5-fluorobenzene (467 mg, 2.23 mmol) in degassed 1,4-dioxane (2ml), was added TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (69.6 mg, 0.08 mmol). The suspension was heated in a sealed container up to 95°C for 16hours. The reaction mixture was filtered through a short pad of dicalite, concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 0 to 8 % iPrOH in CH2Cl2. The solvent was evaporated to dryness to afford the 8-(1-(3-chloro-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (375 mg, 78 %). The product triturated with diethyl ether - CH2Cl2 (9-1) and the desired compound was filtered and dried to afford 320 mg of product P1 as a clear yellow solid. However the final sample product contain some diethyle ether which was removed under vacuum O/N before sample submission. |
Here is a chemical reaction formula: Reactants are:aryl halide:CC(C)(C)OC(=O)C1=CC=C(C=C1)Br;amine:CCOC(=O)C1CCNCC1, 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:CCOC(=O)C1CCN(CC1)C2=CC=C(C=C2)C(=O)OC(C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1\. To a microwave tube was added tert-butyl 4-bromobenzoate (1.328 g, 5.16 mmol), ethyl piperidine-4-carboxylate (1.000 g, 5.16 mmol), Cs2CO3 (5.05 g, 15.49 mmol), Pd2dba3 (0.473 g, 0.52 mmol), and BINAP (0.643 g, 1.03 mmol). The mixture was dissolved in [Solvents] and sealed. The tube was de-gassed and inflated with N2. 2\. The reaction was heated at 110°C in oil-bath overnight. LCMS showed reaction complete. The reaction mixture was filter through celite pad and the solution was loaded to column for a ISCO purification (30% EtOAc in Hex). The purification is difficult with multiple by-products. Several ISCO purification was carried out and fractions were combined with other batches. Yield was poor. |
Here is a chemical reaction formula: Reactants are:amine:C1CNCCN1;aryl halide:C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3)N4C=NC5=C4C=CC=C5Br, 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.C(Cl)(Cl)Cl.[Pd].[Pd], and Products are 0:C1CN(CCN1)C2=CC=CC3=C2N=CN3C(C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 2.0-5.0 mL microwave vial was charged with 4-bromo-1-trityl-1H-benzo[d]imidazole (300 mg, 0.68 mmol), Sodium tert- butoxide (92 mg, 0.96 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (25.5 mg, 0.04 mmol), Piperazine (0.321 mL, 4.10 mmol) and toluene (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (14.14 mg, 0.01 mmol) was added. The reaction mixture was stirred at 90°C under microwave irradiation for 1h. The solution was diluted with EtOAc and washed with water, saturated NaHCO3 solution, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced vacuum. The crude material was loaded on a 24g silica gel column and purified on a Teledyne Isco instrument, eluting with 10 : 1 / DCM : MeOH containing 0.2% ammonium hydroxide (v/v) to provide 4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole (130 mg, 42.8 %) as a solid. The product was analyzed by analytical HPLC MS using the high pH gradient method (mobile phase: 5-95% B; A: H2O with 10 mM NH5CO3 and 0.375% NH4OH v/v, B: MeOH, 2.25 min run) on X-Bridge C18, 2.1 x 30 mm, 5 mm particle size. MS _m/z_ 445.6 [M+H]\+ (ESI), Rt 2.61 min; 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.64 (br. s., 1 H), 3.11 - 3.22 (m, 4 H), 3.48 - 3.59 (m, 4 H), 6.08 (d, J=8.20 Hz, 1 H), 6.54 (d, J=7.42 Hz, 1 H), 6.79 (t, J=8.01 Hz, 1 H), 7.13 - 7.23 (m, 6 H), 7.30 (d, J=3.91 Hz, 9 H), 7.79 (s, 1 H). |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1C(F)(F)F)Br)F;amine:CC(C)(C)OC(=O)N1CCNCC1, 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=C(C=CC(=C2)C(F)(F)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 250 mL round flask was charged with 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (1.016 g, 4.18 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.260 g, 0.42 mmol), Sodium tert-butoxide (0.482 g, 5.02 mmol), tert-butyl piperazine-1-carboxylate (0.779 g, 4.18 mmol) and a mixture of toluene (25 mL) and DMF (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0) (0.191 g, 0.21 mmol) was added. The reaction mixture was stirred at 105°C in an oil bath 12h. The solution was diluted with EtOAc and washed with saturated NaHCO3 solution, brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The aqueous phase was evaporated and the residue was extracted with EtOAc (3X20mL), concentrated. The combined crude material was loaded on a 80g silica gel column and purified on a Teledyne Isco instrument, eluting with 0% to 25% ethyl acetate in heptane to provide tert-butyl 4-(2-fluoro-5-(trifluoromethyl)phenyl)piperazine-1-carboxylate (0.622 g, 42.7 %) as an oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1C(F)(F)F)Cl;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=NC=CC(=C2)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 250 mL round flask was charged with 2-chloro-4-(trifluoromethyl)pyridine (2.57 g, 14.16 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.881 g, 1.42 mmol), Sodium tert-butoxide (1.633 g, 16.99 mmol), tert-butyl piperazine-1-carboxylate (2.64 g, 14.16 mmol) and a mixture of toluene (25 mL) and DMF (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0) (0.648 g, 0.71 mmol) was added. The reaction mixture was stirred at 105°C in an oil bath 12h. The solution was diluted with EtOAc and washed with saturated NaHCO3 solution, brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The aqueous phase was evaporated and the residue was extracted with EtOAc (3X20mL), concentrated. The combined crude material was loaded on a 80g silica gel column and purified on a Teledyne Isco instrument, eluting with 0% to 25% ethyl acetate in heptane to provide tert-butyl 4-(4-(trifluoromethyl)pyridin-2-yl)piperazine-1-carboxylate (2.164 g, 46.1 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC2=C(C=CC(=C2N=C1)OS(=O)(=O)C(F)(F)F)Cl;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Solvent:C1CCOC1;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=C3C(=C(C=C2)Cl)C=CC=N3, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 5-chloroquinolin-8-yl trifluoromethanesulfonate (1.8 g, 5.78 mmol), Cesium carbonate (2.63 g, 8.09 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.180 g, 0.29 mmol), tert- Butyl 1-piperazinecarboxylate (1.291 g, 6.93 mmol) and Palladium(II) acetate (0.065 g, 0.29 mmol) in THF (30 mL) under a nitrogen atmosphere was stirred at 75 °C for 6h. The solution was cooled to rt and diluted with ether. The mixtture was filtered through celite and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 25-50% EtOAc in heptane, to afford tert-butyl 4-(5-chloroquinolin-8-yl)piperazine-1-carboxylate (0.489 g, 24.34 %) as an oil. 1H NMR (400 MHz, CHLOROFORM- _d_ ) d ppm 1.51 (s, 9 H), 3.28 - 3.37 (m, 4 H), 3.72 - 3.82 (m, 4 H), 7.06 (d, _J_ =7.81 Hz, 1 H), 7.48 - 7.57 (m, 2 H), 8.57 (dd, _J_ =8.59, 1.95 Hz, 1 H), 8.94 (dd, _J_ =4.10, 1.76 Hz, 1 H); MS m/z 348.31 [M+H]+ (ESI). |
Here is a chemical reaction formula: Reactants are:aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC(=O)NC1=C(C=CC(=C1)N)N(C)CCCN(C)C, 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: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:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)N(C)CCCN(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (70mg, 0.30 mmol), N-(5-amino-2-((3-(dimethylamino)propyl)(methyl)amino)phenyl)acetamide (79 mg, 0.30 mmol), and cesium carbonate (195 mg, 0.60 mmol) in DMA (0.5 mL) (),Pd2(dba)3 (13.72 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.33 mg, 0.03 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS comletion. MeOH (2 mL) was added to the reaction mixture. filtered. The mother liquid solvent was removed by ratovapor to yield sticky oil. The crude product was loaded on ISCO (Hex to Hex:EtOAc To EtOAc to EtOAc:MeOH=10:1) to give sticky oil. The product was not pure. It was purified by to give N-(5-(3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-((3-(dimethylamino)propyl)(methyl)amino)phenyl)acetamide (50.0 mg, 29.0 %) as TFA salt NMR and LCMS showed desired product, see attachment. |
Here is a chemical reaction formula: Reactants are:m2:C1(=CC=CC=C1)N=C=S;m1_m3:NC1=CC=C(C(=O)NC2=CC=C(C=C2)N)C=C1, Reagents are:m1_m3:CC(=O)C, and Products are 0:C1(=CC=CC=C1)NC(=S)NC1=CC=C(C(=O)NC2=CC=C(C=C2)NC(NC2=CC=CC=C2)=S)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4,4'-Diaminobenzanilide (0.658 g, 2.5 mM) was dissolved in 20 ml of acetone, and 2 equivalents of phenylisothiocyanate (0.676 g, 5 mM) was added. The mixture was stirred at 55° C. for 10 minutes. After cooling, the reaction mixture was filtered, and washed with acetone/n-hexane to obtain 0.90 g (72.3% yield) of a colorless crystal of compound A-15. |
Here is a chemical reaction formula: Reactants are:m1_m3:NC1=CC=C(C(=O)NC2=CC=C(C=C2)N)C=C1;m2:C(C1=CC=CC=C1)N=C=S, Reagents are:m1_m3:CC(=O)C, and Products are 0:C(C1=CC=CC=C1)NC(=S)NC1=CC=C(C(=O)NC2=CC=C(C=C2)NC(NCC2=CC=CC=C2)=S)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4,4'-Diaminobenzanilide (0.568 g, 2.5 mM) was dissolved in 20 ml of acetone, and 2 equivalents of benzylisothiocyanate (0.746 g, 5 mM) was added. The mixture was stirred at 55° C. for 10 minutes. After cooling, the reaction mixture was filtered, and washed with acetone/n-hexane to obtain 0.57 g (43.4% yield) of a colorless crystal of compound A-16. |
Here is a chemical reaction formula: Reactants are:m1_m3:C1=CC(=CC=C1N)N;m2:C(C1=CC=CC=C1)N=C=S, Reagents are:m1_m3:C(C)(=O)OCC, and Products are 0:C(C1=CC=CC=C1)NC(=S)NC1=CC=C(C=C1)NC(NCC1=CC=CC=C1)=S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: p-Phenylenediamine (2.707 g, 25 mM) was dissolved in 20 ml of ethyl acetate, and 2 equivalents of benzylisothiocyanate (7.461 g, 50 mM) were added. The mixture was stirred at 80° C. for 30 minutes. After cooling, the reaction mixture was filtered, and washed with ethylacetate/n-hexane to obtain 6.26 g (61.6% yield) of a colorless crystal of compound A-25. |
Here is a chemical reaction formula: Reactants are:m1_m3:CC1=C(C=C(C(=C1)N)C)N;m2:C(C1=CC=CC=C1)(=O)N=C=S, Reagents are:m1_m3:C(C)(=O)OCC, and Products are 0:C(C1=CC=CC=C1)(=O)NC(=S)NC1=C(C=C(C(=C1)C)NC(NC(C1=CC=CC=C1)=O)=S)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2,5-Dimethyl-p-phenylenediamine (0.340 g, 2.5 mM) was dissolved in 30 ml of ethyl acetate, and 2 equivalents of benzoylisothiocyanate (0.816 g, 5 mM) were added. The mixture was stirred at room temperature for 10 minutes. After cooling, the reaction mixture was filtered, and washed with ethyl acetate/n-hexane to obtain 1.14 g (98.6% yield) of a colorless crystal of compound A-26. |
Here is a chemical reaction formula: Reactants are:m2:C(C1=CC=CC=C1)N=C=S;m1_m3:C1(=CC=CC=2C(=CC=CC12)N)N, Reagents are:m1_m3:C(C)(=O)OCC, and Products are 0:C(C1=CC=CC=C1)NC(=S)NC1=CC=CC2=C(C=CC=C12)NC(NCC1=CC=CC=C1)=S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1,5-Naphthalenediamine (0.791 g, 5 mM) was dissolved in 20 ml of ethyl acetate, and 2 equivalents of benzylisothiocyanate (1.492 g, 10 mM) were added. The mixture was stirred at 80° C. for 30 minutes. After cooling, the reaction mixture was filtered, and washed with ethylacetate/n-hexane to obtain 0.70 g (30.7% yield) of a colorless crystal of compound A-29. |
Here is a chemical reaction formula: Reactants are:m3_m0:OCC(O)CO;m1_m2:O;m1_m2:O, Reagents are:, and Products are 0:OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A gel vehicle containing about 25-28% water (apart from water provided as humectant solvent), about 10-12% of 99.5% glycerine solution and about 30-35% of 70% sorbitol solution can readily provide a refractive index of about 1.43 to 1.46 and permit formation of a clear gel dentifrice in which the refractive index of the polishing agent is about 1.41 to 1.47 and within 0.02 of the refractive index of the liquid vehicle. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=CC=C(C(C(=O)O)=C1)O;m1_m2:S(O)(O)(=O)=O;m3:CO, Reagents are:, and Products are 0:ClC1=CC=C(C(C(=O)OC)=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-Chlorosalicylic acid was treated with one equivalent of 18M sulfuric acid in refluxing methanol for 20 h to give methyl 5-chlorosalicylate. After recrystallization from isopropyl ether the salicylate was treated with the sodium salt of N-chloro-p-toluylsulfonamide in dimethylformamide in the presence of an excess of sodium iodide to give methyl 5-chloro-3-iodosalicylate. Treatment with 2-bromoethanol in refluxing acetone in the presence of an excess of potassium carbonate for 10 h gave methyl 5-chloro-3-iodo-2-(2-hydroxyethoxy)benzoate which was subsequently hydrolyzed in ethanol containing 3N NaOH to give 5-chloro-3-iodo-2-(2-hydroxyethoxy)benzoic acid. The acid was treated with 1,1-carbonyldiimidazole in DMF for 1 h, the resulting imidazole amide condensed with (S)-3-aminoquinuclidine. The resulting substituted chlorobenzamide was purified by acid-base extractions and the hydroxy group was protected by a toluenesulfonyl group. The tosylate can be reacted with 50 mCi of hydro[18F]fluoric acid, prepared from H2 [18O]O in an 11 MeV cyclotron and K2CO3 -kryptofix[222] in acetonitrile for 20 min at 120° C. and purified by HPLC, to produce the radiochemical pure product of [18F]-18. |
Here is a chemical reaction formula: Reactants are:m3:N#CN;m2:C(C)(=O)O;m1:C(C)NCCCOC;m0_m4:C(C)(=O)[O-], Reagents are:, and Products are 0:COCCCN(C(=N)N)CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 3.00 g (25.6 mmol) of N-ethyl-3-methoxypropylamine and 1.54 g (25.6 mmol) of acetic acid were placed in a 50 ml two neck flask. While heating the flask in a 90° C. oil bath, 1.08 g (25.6 mmol) of cyanamide was added. After 12 hours of the reaction, the product was purified by a silica gel column chromatography (eluent, chloroform/ethanol=1/2 containing 0.5% acetic acid) to obtain 2.80 g of the title compound (wax-like, 12.8 mmol, 50.0% in yield) in the form of acetate. Results of the analysis of this compound are as follows. |
Here is a chemical reaction formula: Reactants are:m2:C(C)(=O)O;m1:COCCOCCN;m0_m4:C(C)(=O)[O-];m3:N#CN, Reagents are:, and Products are 0:COCCOCCNC(=N)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5.96 g (50.0 mmol) of 2-(2-methoxyethoxy)ethylamine and 3.00 g (50.0 mmol) of acetic acid were placed in a 30 ml two neck flask. While heating the flask in a 90° C. oil bath, 3.10 g (73.7 mmol) of cyanamide was added. After 5 hours of the reaction, the product was purified by a silica gel column chromatography (eluent, chloroform/ethanol=2/1 containing 0.5% acetic acid) to obtain 3.15 g of the title compound (wax-like, 14.2 mmol, 28.5% in yield) in the form of acetate. Results of the analysis of this compound are as follows. |
Here is a chemical reaction formula: Reactants are:m3:N#CN;m1:C(C1=CC=CC=C1)(=O)OCCOCCN;m0_m4:C(C)(=O)[O-];m2:C(C)(=O)O, Reagents are:, and Products are 0:C(C1=CC=CC=C1)(=O)OCCOCCNC(=N)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2.14 g (10.2 mmol) of 2-(2-aminoethoxy)ethyl benzoate and 0.624 g (10.4 mmol) of acetic acid were placed in a 50 ml two neck flask. While heating the flask in a 90° C. oil bath, 0.680 g (16.2 mmol) of cyanamide was added. After 6 hours of the reaction, the product was purified by a silica gel column chromatography (eluent, chloroform/ethanol=1/2 containing 0.5% acetic acid) to obtain 1.97 g of the title compound (wax-like, 6.33 mmol, 62.0% in yield) in the form of acetate. Results of the analysis of this compound are as follows. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4_m0:CCCCCC;m1_m2_m3_m4_m0:C1=CC=CC=C1;m1_m2_m3_m4_m0:C1(=CC=CC=C1)C, Reagents are:m1_m2_m3_m4_m0:CC=1C=CC(=CC1)C, and Products are 0:CCCCCCCCCCCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: When the dispersion of the solid polymer electrolyte was added to organic solvents having a dielectric constant of less than 3, such as n-hexane, benzene, toluene, p-xylene and dodecane having dielectric constants of 1.89, 2.28, 2.38, 2.27 and 2.02, respectively, the solid polymer electrolyte produced a white precipitate and the polarization characteristics of the cells could hardly be taken out. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:C(C)[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](NC(=O)OCC1=CC=CC=C1)C(C(O)=O)CC1=CC=CC=C1)=O)[C@@H](OCC1=CC=CC=C1)C)=O;m1_m3_m2_m4:C(C)(=O)O, Reagents are:m1_m3_m2_m4:CO;m1_m3_m2_m4:[Pd].[C], and Products are 0:C(C)[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)[C@@H](O)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 5.30 g (8.0 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-O-benzyl-D-threonine (S)-α-ethylbenzylamide in 150 ml of methanol were added 1.0 ml of acetic acid and 3.0 g of 5% Pd-carbon (water content 50%), and the mixture was reduced under hydrogen overnight at room temperature and then at 50° C. for 3 hours. The catalyst was removed by filtration, the resulting filtrate was concentrated under reduced pressure, and the residue was crystallized from water to obtain 1.60 g (4.6 mmols) of α-L-aspartyl-D-threonine (S)-α-ethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m5_m3_m4:C(C1=CC=CC=C1)OC(=O)N[C@@H](C(C(O)=O)CC1=CC=CC=C1)C(=O)N[C@H]([C@H](C)CC)C(=O)O;m1_m2_m5_m3_m4:C(C)[C@@H](C1=CC=CC=C1)N;m1_m2_m5_m3_m4:O;m1_m2_m5_m3_m4:C=1C=CC2=C(C1)N=NN2O, Reagents are:m1_m2_m5_m3_m4:C(Cl)Cl, and Products are 0:C(C)[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](NC(=O)OCC1=CC=CC=C1)C(C(O)=O)CC1=CC=CC=C1)=O)[C@H](C)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 6.69 g (14.2 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine and 2.04 g (15.1 mmols) of (S)-α-ethylbenzylamine in 200 ml of methylene chloride were added 2.73 g (14.2 mmols) of water-soluble carbodiimide hydrochloride and 1.92 g (14.2 mmols) of HOBt under cooling and stirred for one hour under cooling and then overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and 150 ml of ethyl acetate was added. The resulting residue was washed two times each with 70 ml of aqueous 5% citric acid, once with 70 ml of water, two times each with 70 ml of aqueous 5% sodium hydrogencarbonate and once with 70 ml of brine in that order. The resulting organic layer was dried with anhydrous magnesium sulfate, the magnesium sulfate was removed by filtration, and the resulting filtrate was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and concentrated under reduced pressure. The resulting solid residue was washed with ethyl acetate and dried to obtain 2.81 g (4.7 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine (S)-α-ethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](NC(=O)OCC1=CC=CC=C1)C(C(O)=O)CC1=CC=CC=C1)=O)[C@H](C)CC)=O, Reagents are:m4:[Pd].[C];m1_m2_m3:CO;m1_m2_m3:O, and Products are 0:C(C)[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)[C@H](C)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of 2.81 g (4.7 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine (S)-α-ethylbenzylamide in 150 ml of methanol and 50 ml of water was added 2.0 g of 10% Pd-carbon (water content 50%). The mixture was reduced under hydrogen at room temperature for 5 hours. The catalyst was removed by filtration, and the resulting filtrate was concentrated under reduced pressure to be 20 ml. The crystals thus precipitated were taken out by filtration and dried to obtain 1.22 g (3.4 mmols) of α-L-aspartyl-D-isoleucine (S)-α-ethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m5_m6:O;m5_m6:C=1C=CC2=C(C1)N=NN2O;m1_m2:Cl.O1CCOCC1;m1_m2:C(C)[C@@H](C1=CC=CC=C1)NC(C(NC(=O)OC(C)(C)C)(CC)CC)=O;m3_m4:C(C)N(CC)CC;m3_m4:C(C1=CC=CC=C1)C([C@H](NC(=O)OCC1=CC=CC=C1)C(=O)[O-])C(=O)[O-], Reagents are:, and Products are 0:C(C)[C@@H](C1=CC=CC=C1)NC(C(NC([C@@H](N)CC(O)=O)=O)(CC)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 19 ml of 4N-HCl/dioxane solution were added to 1.31 g (3.76 mmols) of N-t-butoxycarbonyl-α,α-diethylglycine (S)-α-ethylbenzylamide, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, 30 ml of ether was added to the residue, and this was again concentrated. The residue was dissolved in 25 ml of methylene chloride, and 0.55 ml (4.13 mmols) of triethylamine and 1.48 g (4.13 mmols) of β-benzyl-N-benzyloxycarbonyl-L-aspartate were added thereto. Under cooling, 0.79 g (4.13 mmols) of water-soluble carbodiimide hydrochloride and 0.51 g (3.76 mmols) of HOBt were added thereto, and these were stirred for one hour under cooling and then overnight at room temperature. The reaction mixture was concentrated under reduced pressure and 50 ml of aqueous 5% citric acid were added. The resulting residue was extracted two times each with 50 ml of ethyl acetate and then washed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order. The resulting organic layer was dried with anhydrous magnesium sulfate and filtered, and the resulting filtrate was concentrated under reduced pressure. The residue was dissolved in 30 ml of methanol, 0.30 g of 10% Pd-carbon (water content 50) was added thereto, and the mixture was reduced under hydrogen. 40 ml of water was added to this, the catalyst was removed by filtration, and the resulting filtrate was concentrated to about 1/4. This was then stored in a refrigerator overnight. The crystal thus precipitated was removed by filtration and dried to obtain 0.40 g (1.10 mmols) of α-L-aspartyl-α,α-diethylglycine (S)-α-ethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m1_m2:Cl.O1CCOCC1;m1_m2:C(C)(C)(C)OC(=O)N[C@H](C1=CC=CC=C1)COC, Reagents are:, and Products are 0:Cl.COC[C@@H](C1=CC=CC=C1)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 60 ml of 4N-HCl/dioxane solution was added to 4.02 g (16.0 mmols) of N-t-butoxycarbonyl-(R)-α-methoxymethylbenzylamine, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure. 30 ml of ether were added to the residue, and this was further concentrated to obtain (R)-α-methoxymethylbenzylamine hydrochloride in quantitative yield. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](NC(=O)OCC1=CC=CC=C1)C(C(O)=O)CC1=CC=CC=C1)=O)C(C)C)=O, Reagents are:m1_m2_m3:CO;m1_m2_m3:O;m4:[Pd].[C], and Products are 0:COC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)C(C)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of 6.20 g (10.5 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-valine (R)-α-methoxymethylbenzylamide in 200 ml of methanol and 50 ml of water was added 1.50 g of 10% Pd-carbon (water content 50%). The mixture was reduced under hydrogen under heat at 40° C. The catalyst was removed by filtration, and the resulting filtrate was concentrated under reduced pressure to 15 ml. The crystal thus precipitated was removed by filtration and dried to obtain 2.69 g (7.36 mmols, 70.0% ) of α-L-aspartyl-D-valine (R)-α-methoxymethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m1_m2:Cl.O1CCOCC1;m1_m2:C(C)(C)(C)OC(=O)N[C@H](C1=CC=CC=C1)COCC, Reagents are:, and Products are 0:Cl.C(C)OC[C@@H](C1=CC=CC=C1)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 12.5 ml of 4N-HCl/dioxane solution were added to 0.66 g (2.5 mmols) of N-t-butoxycarbonyl-(R)-α-ethoxymethylbenzylamine, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, 30 ml of ether was added to the residue, and this was further concentrated to obtain (R)-α-ethoxymethylbenzylamine hydrochloride at a quantitative yield. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)OC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](NC(=O)OCC1=CC=CC=C1)C(C(O)=O)CC1=CC=CC=C1)=O)C(C)C)=O, Reagents are:m1_m2_m3:CO;m1_m2_m3:O;m5:O;m4:[Pd].[C], and Products are 0:C(C)OC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)C(C)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of 1.20 g (1.99 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-valine (R)-α-ethoxymethylbenzylamide in 50 ml of methanol and 10 ml of water was added 0.30 g of 10% Pd-carbon (water content 50%). The mixture was reduced under hydrogen under heat at 40°C., 40 ml of water was added thereto, the catalyst was removed by filtration, and the resulting filtrate was concentrated under reduced pressure to 5 ml. The crystal thus precipitated was removed by filtration and dried to obtain 0.38 g (1.00 mmol, 50.3%) of α-L-aspartyl-D-valine (R)-α-ethoxymethylbenzylamide. |
Here is a chemical reaction formula: Reactants are:m1:C(C1=CC=CC=C1)OC(=O)N[C@@H](C(C(O)=O)CC1=CC=CC=C1)C(=O)N[C@H]([C@H](C)CC)C(=O)O;m2:Cl.COC[C@@H](C1=CC=CC=C1)N, Reagents are:, and Products are 0:COC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)[C@H](C)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The same process as in Example 15 was repeated, except that N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine was used in place of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-valine and that (R)-α-methoxymethylbenzylamine hydrochloride was used in place of (R)-α-ethoxymethylbenzylamine hydrochloride, and α-L-aspartyl-D-isoleucine (R)-α-methoxymethylbenzylamide was obtained as a solid product. The total yield was 22.1%. |
Here is a chemical reaction formula: Reactants are:m1:C(C1=CC=CC=C1)OC(=O)N[C@@H](C(C(O)=O)CC1=CC=CC=C1)C(=O)N[C@H](C)C(=O)O;m2:Cl.COC[C@@H](C1=CC=CC=C1)N, Reagents are:, and Products are 0:COC[C@@H](C1=CC=CC=C1)NC([C@H](NC([C@@H](N)CC(O)=O)=O)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The same process as in Example 15 was repeated, except that N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-alanine was used in place of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-valine and that (R)-α-methoxymethylbenzylamine hydrochloride was used in place of (R)-α-ethoxymethyl benzylamine hydrochloride, and α-L-aspartyl-D-alanine-(R)-α-methoxymethylbenzylamide was obtained as a solid product. The total yield was 57.3%. |
Here is a chemical reaction formula: Reactants are:m2_m4:[Cl-].[Ca+2].[Cl-];m1_m3:P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+], Reagents are:m5:O;m2_m4:O;m1_m3:O, and Products are 0:P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2].[Ca+2].P(=O)([O-])([O-])[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 78.6 Grams of sodium phosphate were dissolved in 300 grams of water. In a separate beaker, 45.3 grams of calcium chloride were dissolved in 300 grams of water. 200 Grams of each of the above solutions were added simultaneously to 200 grams of water, while being sheared at speeds of 12,000 rpm. This shearing was accomplished since the viscosity resulting from the in situ formation of tricalcium phosphate (TCP) particulates needs to be broken down into submicron size in order to be more effective as a stabilizer. The amount of in situ TCP generated in this Example was 21.3 grams. |
Here is a chemical reaction formula: Reactants are:m2_m4:[Cl-].[Ca+2].[Cl-];m1_m3:P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+], Reagents are:m2_m4:O;m1_m3:O;m5:O, and Products are 0:P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2].[Ca+2].P(=O)([O-])([O-])[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 78.6 Grams of sodium phosphate were dissolved in 300 grams of water. In a separate beaker, 45.3 grams of calcium chloride were dissolved in 300 grams of water. 200 Grams of each of the above solutions were added simultaneously to 200 grams of water, while being sheared at speeds of 12,000 rpm. This shearing was necessary, since the viscosity resulting from the in situ formation of tricalcium phosphate (TCP) particulates needs to be to be broken down into submicron size in order to be effective as a stabilizer. The amount of in situ TCP generated in this Example was 21.3 grams |
Here is a chemical reaction formula: Reactants are:m2_m4:[Cl-].[Ca+2].[Cl-];m1_m3:P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+], Reagents are:m5:O;m2_m4:O;m1_m3:O, and Products are 0:P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2].[Ca+2].P(=O)([O-])([O-])[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 78.6 Grams of sodium phosphate (TCP) were dissolved in 300 grams of water. In a separate beaker, 45.3 grams of calcium chloride were dissolved in 300 grams of water. 200 Grams of each of the above solutions were added simultaneously to 200 grams of water, while being sheared at speeds of 12,000 rpm. This shearing was accomplished once the viscosity resulting from the in situ formation of tricalcium phosphate (TCP) particulates needs to be broken down into submicron size in order to be effective as a stabilizer. The amount of in situ TCP generated in this case was 21.3 grams. |
Here is a chemical reaction formula: Reactants are:m1_m3_m7:P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+];m2_m4_m6:[Cl-].[Ca+2].[Cl-], Reagents are:m1_m3_m7:O;m1_m3_m7:O;m2_m4_m6:O;m2_m4_m6:O;m5:O, and Products are 0:P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2].[Ca+2].P(=O)([O-])([O-])[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 39.3 Grams of sodium phosphate were dissolved in 150 grams of water (Solution A). In a separate beaker, 22.65 grams of calcium chloride were dissolved in 150 grams of water (Solution B). Each of the above solutions were added simultaneously to 200 grams of water, while being sheared at speeds of 12,000 rpm. This shearing was necessary since the viscosity resulting from the in situ formation of tricalcium phosphate (TCP) particulates needs to be broken down into submicron size in order to be effective as a stabilizer. The amount of in situ TCP generated in this case was 16.0 grams. |
Here is a chemical reaction formula: Reactants are:m6_m1_m2_m3_m4:OC1=CC=C(C=O)C=C1;m6_m1_m2_m3_m4:BrCCC1OCCCO1;m6_m1_m2_m3_m4:[I-].[K+];m6_m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+], Reagents are:m5:C(C)(=O)OCC;m6_m1_m2_m3_m4:C(C)#N, and Products are 0:O1C(OCCC1)CCOC1=CC=C(C=O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 500 ml flask, 120 ml of acetonitrile, 13.8 g of 4-hydroxybenzaldehyde, 21.1 g of 2-(2-bromoethyl)-1,3-dioxane, 1.8 g of potassium iodide, and 35.8 g of potassium carbonate were placed and then, reacted at 80° C. for 5 hrs. Thereafter, 200 ml of ethyl acetate was added to the reaction mixture and washed once with a saturated aqueous potassium carbonate solution, distilled water, and saturated saline. The washed organic phase was dried over anhydrous magnesium sulfate and removed solvent, to give 25.6 g of 4-(2-[1,3]-dioxane-2-yl-ethoxy)benzaldehyde. |
Here is a chemical reaction formula: Reactants are:m2_m4:O1C(OCCC1)CCOC1=CC=C(C=O)C=C1;m1:CC(C)([O-])C.[K+], Reagents are:m2_m4:CCOCC;m3:[Br-].C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1;m5:CCOCC, and Products are 0:C(=C)C1=CC=C(OCCC2OCCCO2)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In another 2 liter flask, 57.2 g of methyl triphenylphosphonium bromide was placed. 500 ml of anhydrous ether was poured and then, stirred. To the resulting solution was slowly added 18.0 g of potassium tert-butoxide and reacted at room temperature for 3 hrs. 25.6 g of the above 4-(2-[1,3]-dioxane-2-yl-ethoxy)benzaldehyde was dissolved in 200 ml of anhydrous ether and was slowly added to the reaction mixture and then subjected to reaction at room temperature for 4 hrs. After completion of the reaction, the produced solid by-product was filtered off and washed with distilled water and saturated saline. The organic phase washed was dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure. The reaction mixture was purified by Silica gel column chromatography to obtain 19.7 g of 2-[2-(4-vinylphenoxy)ethyl]-[1,3]-dioxane, represented by the following formula: ##STR9## |
Here is a chemical reaction formula: Reactants are:m6_m1_m2_m3_m4:OC1=CC=C(C=O)C=C1;m6_m1_m2_m3_m4:BrCCC1OCCCO1;m6_m1_m2_m3_m4:[I-].[K+];m6_m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+], Reagents are:m5:C(C)(=O)OCC;m6_m1_m2_m3_m4:C(C)#N, and Products are 0:O1C(OCC1)CCOC1=CC=C(C=O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 500 ml flask, 120 ml of acetonitrile, 13.8 g of 4-hydroxybenzaldehyde, 19.9 g of 2-(2-bromoethyl)-1,3-dioxane, 1.8 g of potassium iodide, and 35.8 g of potassium carbonate were placed and then, reacted at 80° C. for 5 hr. Thereafter, to the reaction mixture was added 200 ml of ethyl acetate and washed once with a saturated aqueous potassium carbonate solution, distilled water and saturated saline. The washed organic phase was dried over anhydrous magnesium sulfate and the solvent was removed, to give 23.7 g of 4-(2-[1,3]-dioxolan-2-yl-ethoxy)benzaldehyde. |
Here is a chemical reaction formula: Reactants are:m2_m4:O1C(OCC1)CCOC1=CC=C(C=O)C=C1;m1:CC(C)([O-])C.[K+], Reagents are:m5:CCOCC;m2_m4:CCOCC;m3:[Br-].C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1, and Products are 0:C(=C)C1=CC=C(OCCC2OCCO2)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In another 2 liter flask, 57.2 g of methyl triphenylphosphonium bromide was placed. 500 ml of anhydrous ether was poured and then, stirred. To the resulting solution was slowly added 18.0 g of potassium tert-butoxide and reacted at room temperature for 3 hrs. 23.7 g of the above 4-(2-[1,3]-dioxolan-2-yl-ethoxy)benzaldehyde was dissolved in 200 ml of anhydrous ether and was slowly added to the reaction mixture and then subjected to reaction at room temperature for 4 hrs. After completion of the reaction, the produced solid by-product was filtered off and washed with distilled water and saturated saline. The organic phase washed was dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure. The reaction mixture was purified by Silica gel column chromatography to obtain 20.8 g of 2-[2-(4-vinylphenoxy)ethyl]-[1,3]-dioxolan, represented by the following formula: ##STR10## |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C1=C(C=CC=C1O)C;m1_m2_m3:OCC1=CC(=CC(=C1O)CO)C;m1_m2_m3:O.O.C(C(=O)O)(=O)O;m5:C=O;m4:CCOCCOC(=O)C, Reagents are:m6:O, and Products are 0:C=1(C(=CC=CC1O)C)C=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A phenolic resin rich in alternating phenolic copolymer block segments was formed by reacting a mixture of 519.0 g of 99 percent pure m-cresol, 538.2 g of 97 percent pure 2,6-bis(hydroxymethyl)-p-cresol and 20 g oxalic acid dihydrate in a solvent mixture of 40 ml deionized water and 200 ml ethyl cellosolve acetate. The reaction mixture was heated to about 70° C. to initiate the reaction forming the alternating copolymer. At 102° C., 32.6 g of 36.9 percent formaldehyde was added in 8 minutes to the reaction mixture to form substantially m-cresol formaldehyde block segments and to chemically bond these segments to the previously formed alternating copolymer. After heating the mixture at reflux for three hours, the amount of heat was increased to remove the water and solvent by distillation. Partial vacuum was applied at about 220° C. and gradually increased to 4 mm Hg to remove the unreacted monomers. Maximum mixture temperature during vacuum stripping was about 226° C. The copolymer was poured from the reaction kettle and allowed to cool. About 840 g of a block copolymer having a number average molecular weight number, Mn, of 1241 Daltons and a Tg of 112° C. were obtained. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:OC1=CC=C(C=C1)C1(C2=CC=CC=C2C=2C=CC=CC12)C1=CC=C(C=C1)O;m1_m2_m3:C1(OCCO1)=O;m1_m2_m3:C([O-])([O-])=O.[K+].[K+];m4_m5:C1COCCOCCOCCOCCOCCO1, Reagents are:, and Products are 0:OCCOC1=C(C=CC=C1)C1=CC=CC=2CC3=CC=CC=C3C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 84.4 g (0.241 mol) of 9,9-bis(4-hydroxyphenyl)fluorene, 46.7 g (0.53 mol) of ethylene carbonate, 3.3 g (0.024 mol) of potassium carbonate, and a catalytic amount of 18-crown-6 in 400 mL of xylenes was heated at reflux with mechanical stirring for 6 h. The mixture was allowed to cool slowly to room temperature, and the solvent was decanted from the precipitated product. The resulting white solid was washed with ligroin (to prevent the formation of a gummy mass), and dried under a stream of nitrogen. The product was recrystallized from methanol, providing 70.4 g (67%) of a white powder. |
Here is a chemical reaction formula: Reactants are:m1:Cl.NC(CCCCN)C(=O)O;m3:P(=O)(O)(O)[O-].[K+];m2:S(=O)(=O)([O-])[O-].[NH4+].[NH4+];m5:Cl;m4:S(=O)(=O)([O-])[O-].[Mg+2], Reagents are:, and Products are 0:Cl.N[C@H](CCCCN)C(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Into a shaking flask having a volume of 500 ml was charged 100 ml of a medium (pH 7.0) comprising 2% of DL-lysine monohydrochloride, 0.2% of ammonium sulfate, 0.1% of potassium dihydrogen phosphate, 0.05% of magnesium sulfate and 0.02% of a yeast extract, and the medium was sterilized at 120° C. for 10 minutes. A loopful of Yarrowia lipolytica IFO 1209 was inoculated into the medium, and cultured at 30° C. for 168 hours with shaking. The cell was removed by centrifuging 1000 ml of the above culture broth to obtain a supernatant. After the supernatant was adjusted to have pH 6.0 with hydrochloric acid, ultrafiltration was carried out in order to remove protein and others, whereby a filtrate was obtained. After activated carbon was added to the filtrate to effect decolorization, the filtrate was concentrated under reduced pressure, and 200 ml of ethanol was added to 20 g of the concentrate to obtain 5.8 g of D-lysine monohydrochloride as crude crystals. 5.8 ml of water was added to the crude crystals, and the crude crystals were dissolved by heating, and then recrystallized by cooling to obtain 2.9 g of crystals of D-lysine monohydrochloride. |
Here is a chemical reaction formula: Reactants are:m2:N[C@@H](CCCCN)C(=O)O;m1:Cl.NC(CCCCN)C(=O)O, Reagents are:, and Products are 0:Cl.N[C@H](CCCCN)C(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Into a shaking flask having a volume of 500 ml was charged ml of a medium (pH 7.0) comprising 0.5% of DL-lysine monohydrochloride, 1.0% of polypeptone, 1.0% of a yeast extract and 0.5% of sodium chloride, and the medium was sterilized at 120° C. for 10 minutes. A loopful of Pseudomonas sp. ATCC 14676 was inoculated into the medium and cultured at 30° C. for 20 hours. The cell collected from 1000 ml of the above culture broth by centrifugation was suspended in a physiological saline and then collected by centrifugation. To the cell was added 500 ml of a 50 mM phosphate buffer (pH 7.0) containing 50 g of DL-lysine monohydrochloride, and the mixture was reacted at 30° C. for 72 hours to degrade L-lysine completely. After the reaction, the cells were removed by centrifugation, and subsequent procedures were carried out in the same manner as in Example 1 to obtain 14.2 g of D-lysine monohydrochloride. |
Here is a chemical reaction formula: Reactants are:m3:CN(C=O)C;m1_m5:BrC=1C=C(C2=C(C(CCS2)(C)C)C1C)C;m4:Cl;m2:C(CCC)[Li], Reagents are:m1_m5:C(C)OCC, and Products are 0:CC1(CCSC2=C1C(=C(C=C2C)C=O)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 6-Bromo-3,4-dihydro-4,4,5,8-tetramethyl-2H-1-benzothiopyran (19.8 g, World Patent Application 95/04054) was dissolved in diethyl ether (350 mL) and treated with n-butyllithium (2.5N in hexanes, 42 mL). The mixture was stirred at room temperature for 1 h and then cooled in a dry-ice/acetone bath. Dimethylformamide (16 mL) was added over a period of several minutes and the reaction bath was allowed to warm to -40° C. Hydrochloric acid (1N aqueous, 100 mL) was added and the mixture was allowed to warm to 23° C. The organic phase was separated and washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase was dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using hexanes/ether (9:1) as eluent to afford the desired compound as a yellow semi-solid (7.7 g). 1H NMR(CDCl3): δ 1.5 (6H), 2.0 (2H), 2.3 (3H), 2.8 (3H), 3.0 (2H), 7.4 (1H), 10.2 (1H). |
Here is a chemical reaction formula: Reactants are:m1_m2:C[S-].[Na+];m1_m2:ClC1=NC(=NC(=C1)Cl)OCC1=CC=CC=C1, Reagents are:m3:C1CCOC1, and Products are 0:ClC1=NC(=NC(=C1)SC)OCC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Aqueous sodium thiomethoxide (15%, 2.75 g, 0.0059×1.0 mol) was added dropwise in 4,6-dichloro-2-(phenylmethoxy)pyrimidine (Compound No. II-26) (1.5 g, 0.0059 mol) dissolved in THF at room temperature. After allowed to react for 2 hours, the reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate. The organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated, then purified on a silica gel column to obtain 4-chloro-6-methylthio-2-(phenylmethoxy)pyrimidine (Compound No. II-15) as an intermediate. |
Here is a chemical reaction formula: Reactants are:m4_m0_m1:FC(C=1C=C(C=CC1)O)(F)F;m2_m3:[H-].[Na+];m2_m3:ClC1=NC(=NC=C1)SC, Reagents are:m4_m0_m1:C1CCOC1, and Products are 0:CSC1=NC=CC(=N1)OC1=CC(=CC=C1)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In THF, a phenoxide was prepared from 3-(trifluoromethyl)phenol (4.54 g, 0.0187×1.5 mol) was mixed with NaH (1.12 g (ca. 60% in mineral oil), 0.0187×1.5 mol), and 4-chloro-2-(methylthio)pyrimidine (Compound No. VII-1) (3.0 g, 0.0187 mol) was added thereto and the mixture was refluxed for about 10 hours. The reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate to separate an organic phase. The organic phase was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated, then recrystallized from a methanol/water system to obtain the intermediate compound. |
Here is a chemical reaction formula: Reactants are:m4_m0_m1_m2_m3:FC(C=1C=C(C=CC1)O)(F)F;m4_m0_m1_m2_m3:[H-].[Na+];m4_m0_m1_m2_m3:BrC1=NC(=NC(=C1)Br)SC, Reagents are:m4_m0_m1_m2_m3:C1CCOC1, and Products are 0:BrC1=NC(=NC(=C1)OC1=CC(=CC=C1)C(F)(F)F)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In THF, a phenoxide was prepared from m-(trifluoromethyl)phenol (1.30 g, 0.00794×1.0 mol) and NaH (0.32 g (ca. 60% in mineral oil), 0.00794×1.0 mol), and 4,6-dibromo-2-(methylthio)pyrimidine (Compound No. VII-22) (2.0 g, 0.00794 mol) was added thereto, and the mixture was then allowed to react for 5 hours at room temperature. |
Here is a chemical reaction formula: Reactants are:m2_m8:C(C1=CC=CC=C1)(=O)C(C(=O)OCC)CC#C;m1_m6_m7:[OH-].[Na+];m5:Cl;m3_m4_m9:[OH-].[Na+];m3_m4_m9:CNO, Reagents are:m2_m8:CO;m1_m6_m7:O;m1_m6_m7:CO;m10:CCOCC;m3_m4_m9:O, and Products are 0:CN1OC(C(C1=O)CC#C)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 0.28 g (7.0 mmol) of NaOH in 3 mL of water and 7 mL of methanol was cooled to -30° C. and and a solution of 1.42 g (6.2 mmol) of ethyl α-benzoyl-α-propargylacetate in 2 mL of methanol was added dropwise over 2 min. The mixture was stirred at -30° C. for 10 min and a precooled slurry of 0.54 g (13.5 mmol) of NaOH and 1.02 g (12.2 mmol) of N-methylhydroxylamine in 1.5 mL of water was added in one portion. After the mixture had been stirred at -30° C. for 2 h, a 2 mL portion of conc HCl was added and the mixture was heated at reflux for 1 h. The mixture was allowed to cool to room temperature, diluted-with 150 mL of ether, washed with 50 mL of water and 50 mL of saturated aqueous NaHCO3 and dried. Removal of the solvent on the rotovap left 1.09 g of an oil which was purified by flash chromatography on a column of 30 g of silica gel eluted successively with 100 mL portions of 20, 30, 40, 50, 60, 70 and 80% ether in hexanes to afford 0.46 g of 2-methyl-5-phenyl-4-propargylisoxazolin-3-one (Compound 1) as a white solid, m.p. 85°-87° C. |
Here is a chemical reaction formula: Reactants are:m1:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C;m2:C(CCC)[Li];m4:Cl;m3:ClC(=O)OC, Reagents are:m8:[Au];m7:[Au];m5:C1CCOC1, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of I g (4.62 mol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 150 mL THF under a nitrogen atmosphere cooled to -78° C. was added dropwise at such a rate as to keep the temperature below -65° C. 4.1 mL (9.48 mmol) 2.32M n-butyllithium in hexanes. The resulting amber turbid solution was stirred at -78° C. for ca. 30 minutes. Methyl chloroformate (0.37 mL, 4.86 mmol) was added in one portion and the resulting gold reaction mixture was allowed to warm to room temperature and stirred for ca. 1.5 hours. The gold reaction mixture was cooled to 0° C. and acidified with 1N HCl. The THF phase was separated washed with brine, dried (MgSO4) and concentrated to an ember oil. The NMR of the crude reaction product was consistent with the title compound, additionally the NMR indicated that a trace of the starting material was also present. The crude material was combined with the product from a similar reaction run on the scale described below and chromatographed to give the title compound. |
Here is a chemical reaction formula: Reactants are:m2_m6:C(CCC)[Li];m4:Cl;m1_m5:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C;m3:ClC(=O)OC, Reagents are:m7:[Au];m8:[Au];m1_m5:C1CCOC1, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 5 g (23 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 150 mL THF under nitrogen atmosphere cooled to -78° C. was added dropwise, at such a rate as to keep the temperature below -65° C., 20 mL (47.4 mmol) 2.32M n-butyllithium in hexanes. The resulting amber turbid solution was stirred at -78° C. for ca. 30 minutes. 1.87 mL (24.3 mmol) of methyl chloroformate was add in one portion and the resulting gold reaction mixture was allowed to warm to room temperature and stir for ca. 1.5 hours. The gold reaction mixture was cooled to 0° C. and acidified with 1N HCl. The THF phase was separated, washed with brine, dried (MgSO4) and concentrated to an amber oil. The oil was combined with the crude product from the previous example and chromatographed on silica (30% ethyl acetate/70% hexanes) affording 3.53 g of the title compound as a solid. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C(=O)OC;m1_m4_m2:FC(C(=O)O)(F)F, Reagents are:m1_m4_m2:C(Cl)Cl;m3:[Au], and Products are 0:NS(=O)(=O)C1=C(N(C=C1)C)C(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 3.53 g of methyl 3-[[(1,1-dimethylethyl)amino]-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylate in 40 mL, of methylene chloride under an nitrogen atmosphere was added 80 mL of trifluoroacetic acid (TFA). The gold solution was stirred at room temperature overnight ca. 16 hours. The gold solution was concentrated to an oily residue. Diethyl ether was added to the residue and removed by evaporation to remove residual TFA. The resulting solid was suspended in diethyl ether and filtered affording the title compound as a tan solid, m.p. 105°-107° C. |
Here is a chemical reaction formula: Reactants are:m4:Cl;m1_m5:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C;m3:CSSC;m2:C(CCC)[Li], Reagents are:m1_m5:C1CCOC1, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 6.48 g (30 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 150 mL THF under nitrogen atmosphere cooled to -78° C. was added dropwise at such a rate as to keep the temperature below -65° C. 25.52 mL (61.5 mmol) 2.41M n-butyllithium in hexanes. The reaction was stirred at -78° C. for ca. 30 minutes. To the reaction mixture was added 2.97 mL (33 mmol) of dimethyldisulfide in one portion and the resulting reaction mixture was allowed to warm to room temperature and stir for ca. 1.5 hours. The reaction mixture was cooled to 0° C. and acidified with 1N HCl. The THF phase was separated washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue was chromatographed on silica (20% ethyl acetate/80% hexanes) affording 4.63 g of the title compound as an off white solid, m.p. 116°-119° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)SC;m1_m3_m2:FC(C(=O)O)(F)F, Reagents are:m1_m3_m2:C(Cl)Cl, and Products are 0:CN1C(=C(C=C1)S(=O)(=O)N)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4.63 g (17.66 mmol) N-(1,1-dimethylethyl)-1-methyl-2-(methylthio)-1H-pyrrole-3-sulfonamide in 50 mL of methylene chloride was added 50 mL of trifluoroacetic acid (TFA) under a nitrogen atmosphere. The orange reaction mixture was stirred at room temperature overnight ca. 16 hours. The reaction mixture was concentrated to a tan solid. Diethyl ether was added to the tan solid and was removed by evaporation to remove residual TFA. The solid was suspended in diethyl ether and filtered giving 2.9 g of the title compound as a solid, m.p. 135°-137° C. |
Here is a chemical reaction formula: Reactants are:m1_m5:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C;m2_m6:C(CCC)[Li];m4:Cl;m3:BrBr, Reagents are:m1_m5:C(C)OCC, and Products are 0:BrC=1N(C=CC1S(=O)(=O)NC(C)(C)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 8.85 g (41 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 200 mL diethyl ether under a nitrogen atmosphere cooled to -78° C. was added dropwise, at such a rate as to keep the temperature below -65° C., 36.0 mL (85 mmol) 2.41M n-butyllithium in hexanes. The reaction was stirred at -78° C. for ca. 15 minutes. To the reaction mixture was added 2.2 mL (41 mmol) of bromine dropwise. The light orange reaction mixture was allowed to warm to room temperature and stir for ca. 2 hours. The reaction mixture darkened as it stirred at room temperature. The reaction mixture was cooled to 0° C. and acidified with 1N HCl. The ether phase was separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue was chromatographed on silica (25% ethyl acetate/80% hexanes) affording 7.11 g of the title compound as an orange oil. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:BrC=1N(C=CC1S(=O)(=O)NC(C)(C)C)C;m1_m3_m2:C(=O)(C(F)(F)F)O, Reagents are:m1_m3_m2:C(Cl)Cl, and Products are 0:BrC=1N(C=CC1S(=O)(=O)N)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 7.11 g (24 mmol) of 2-bromo-N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 50 mL methylene chloride under a nitrogen atmosphere was added 50 mL of TFA. The reaction mixture was allowed to stir at room temperature overnight ca. 16 hours. The reaction mixture was concentrated in vacuo. Three portions of diethyl ether were added to the crude residue and was removed by evaporation to remove residual TFA, which yielded 1.23 g of the title compound as a light brown solid. |
Here is a chemical reaction formula: Reactants are:m3:Cl;m2:CN(C=O)C;m1_m4:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C, Reagents are:m1_m4:C1CCOC1, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 12.96 g (60 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 300 mL THF under a nitrogen atmosphere cooled to -78° C. was added dropwise, at such a rate as to keep the temperature below -65° C., 52.35 mL (123 mmol) 2.35M n-butylithium in hexanes. The reaction was stirred at -78° C. for ca. 30 minutes. To the reaction mixture was added 4.64 mL (60 mmol) of N,N-dimethylformamide dropwise. The reaction mixture was allowed to warm to room temperature and stir for ca. 2 hours. The reaction mixture was cooled to 0° C. and acidified with 1N HCl. The THF phase was separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue was chromatographed on silica (25% ethyl acetate/80% hexanes) affording 5.72 g of the title compound as a white solid, m.p. 101.5°-103° C. |
Here is a chemical reaction formula: Reactants are:m3:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C=O;m2:C(C)(=O)[O-].[Na+];m4:O;m1_m5:Cl.CON, Reagents are:m1_m5:CO, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(NC=C1)C=NOC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of 3.91 g (46.8 mmol) of methoxyamine hydrochloride in 60 mL of methanol was added 3.84 g (46.8 mmol) of sodium acetate. After stirring the white suspension for ca. 15 minutes 5.72 g (23 mmol) of N-(1,1-dimethylethyl)-2-formyl-1-methyl-1H-pyrrole-3-sulfonamide was added in one portion. The white suspension was heated at a gentle reflux overnight ca. 16 hours. The reaction mixture was cooled to room temperature and poured into 500 mL of water. The aqueous mixture was extracted with four 100 mL portions of methylene chloride. The combined extracts were washed with water, dried (MgSO4) and concentrated in vacuo yielding 5.74 g of the title compound as a white solid, m.p. 99°-101° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:CC(C)(C)NS(=O)(=O)C1=C(NC=C1)C=NOC;m1_m3_m2:C(=O)(C(F)(F)F)O, Reagents are:m1_m3_m2:C(Cl)Cl, and Products are 0:CON=CC=1N(C=CC1S(=O)(=O)N)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 5.74 g (21.9 mmol) of N-(1,1-dimethylethyl)-2-[(methoxyimino)-methyl]-1H-pyrrole-3-sulfonamide in 75 mL methylene chloride under a nitrogen atmosphere was add 75 mL of TFA. The clear orange reaction mixture was allowed to stir at room temperature overnight ca. 16 hours. The orange reaction mixture was concentrated in vacuo. Three portions of diethyl ether were added to the residue and removed by evaporation to remove residual TFA, affording 3.49 g of the title compound as a gray solid, m.p. 120°-122° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:CC(C)(C)C=1C(=C(N(C1)C)S(=O)(=O)N(C)C)S(=O)(=O)N;m1_m3_m2:C(=O)(C(F)(F)F)O, Reagents are:m1_m3_m2:C(Cl)Cl, and Products are 0:CN(S(=O)(=O)C=1N(C=CC1S(=O)(=O)N)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 6.95 g (21 mmol) of N3 -(1,1-dimethylethyl)-N2,N2,1-trimethyl-1H-pyrrole-2,3-disulfonamide in 75 mL of methylene chloride under a nitrogen atmosphere was added 75 mL of TFA. The reaction mixture was allowed to stir at room temperature overnight ca. 16 hours. The reaction mixture was concentrated in vacuo. Three portions of diethyl ether were added to the solid residue and removed by evaporation to remove residual TFA. The solids were suspended in diethyl ether and filtered to yield 4.52 g of the title compound as a solid, m.p. 146°-148° C. |
Here is a chemical reaction formula: Reactants are:m5:Cl;m3_m8:CN(C(=O)Cl)C;m2_m7:C(CCC)[Li];m4:[Cl-].[NH4+];m1_m6:CC(C)(C)NS(=O)(=O)C1=CN(C=C1)C, Reagents are:m3_m8:C1CCOC1;m1_m6:C1CCOC1, and Products are 0:CC(C)(C)NS(=O)(=O)C1=C(N(C=C1)C)C(=O)N(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 6.48 g (30 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 150 mL THF under a nitrogen atmosphere cooled to -78° C. was added dropwise, at such a rate as to keep the temperature below -60° C., 25 mL (61.5 mmol) 2.46M n-butyllithium in hexanes. The reaction mixture was stirred at -78° C. for ca. 30 minutes. To the reaction mixture was added dropwise a solution of 3.1 mL (33 mmol) of N,N-dimethylcarbamyl chloride in 10 mL of THF at such a rate as to maintain the temperature below -65° C. The reaction mixture was allowed to warm to room temperature and stir for ca. 1.5 hours. The reaction mixture was cooled to ca. 5° C. and 60 mL of 50% ammonium chloride solution was added. The reaction mixture was stirred for ca. 15 minutes. The pH was adjusted to ca. 3 with 1N HCl (ca. 30 mL), and the aqueous phase was separated from the THF phase and extracted with ethyl acetate. The combined THF and ethyl acetate extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to an oil. The oil was chromatographed on silica with (20% ethyl acetate/80% n-butyl chloride) affording 4.33 g of the title compound as a pale yellow solid. |