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Here is a chemical reaction formula: Reactants are:m1:BrN1C(CCC1=O)=O;m2:C1(=CC=CC=C1)CC(=O)OC, Reagents are:m4_m3:C(Cl)(Cl)(Cl)Cl;m4_m3:C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O, and Products are 0:BrC(C(=O)OC)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In this example, a mixture containing 5.93 g of N-bromosuccinimide, 5.0 g of methyl phenylacetate; and a catalytic amount (about 0.1 g) of benzoyl peroxide in 50 ml of carbon tetrachloride was warmed to reflux and then refluxed for about 12 hours. The mixture was then cooled to about 0° C. and filtered. The filtrate was concentrated by evaporation under vacuum affording 7.1 g of the title compound as an oil. |
Here is a chemical reaction formula: Reactants are:m2:[Cl-].C[NH3+];m1:BrC(C(=O)OC)C1=CC=CC=C1;m5_m3_m6_m4:C([O-])(O)=O.[Na+];m5_m3_m6_m4:O, Reagents are:m5_m3_m6_m4:[Cl-].C(C1=CC=CC=C1)[N+](CC)(CC)CC;m5_m3_m6_m4:C(Cl)Cl, and Products are 0:CNC(C(=O)OC)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In this example a mixture containing 30.7 g of methyl bromo-phenylacetate, 36.2 g of methyl ammonium chloride (i.e. CH3NH3Cl); 3.0 g of benzyltriethylammonium chloride and 67.5 g of sodium bicarbonate in about 300 ml of methylene chloride (and about 25 ml of water) was warmed to refluxed and refluxed for about 18 hours. The mixture was then cooled and washed three times with water, dried over magnesium sulfate and concentrated by vacuum evaporation affording 17.1 g of the title compound as an oil. |
Here is a chemical reaction formula: Reactants are:m2:BrN1C(CCC1=O)=O;m1:CC1=C(C=CC=C1)C(C(=O)OC)=COC;m3:C1(CCC(N1)=O)=O, Reagents are:m5:C(Cl)(Cl)(Cl)Cl;m4:N(=NC(C#N)(C)C)C(C#N)(C)C, and Products are 0:BrCC1=C(C=CC=C1)C(C(=O)OC)=COC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 20.6 g of the methyl α-(2-methylphenyl)-β-methoxyacrylate obtained as described in method A, 17.65 g of N-bromosuccinimide, 0.2 g of azobisisobutyronitrile and 150 ml of CCl4 are slowly heated to 90° C. and kept at this temperature until all of the succinimide floats on the solvent. The mixture is filtered, the filtrate is evaporated down, and the oil which remains is dissolved in about 5 ml of acetone and brought to crystallization with n-hexane. 27.5 g of colorless crystals of melting point 86°-87° C. are obtained. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC1=C2C=CC(=CC2=CC=C1OC)[C@@H](C(=O)O)C, Reagents are:m1_m2_m3:[OH-].[Na+];m1_m2_m3:[Al].[Ni], and Products are 0:COC=1C=C2C=CC(=CC2=CC1)[C@@H](C(=O)O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 1 g of (S)-2-(5-chloro-6-methoxy-2-naphthyl)-propionic acid in 20 ml of 10% aqueous sodium hydroxide solution at 90° C. is treated with 3 g of a nickel-aluminum alloy in small portions. After stirring the mixture for two hours, it is filtered, diluted with excess dilute hydrochloric acid and extracted with methylene chloride. The organic phase is evaporated to dryness and the residue recrystallized from methylene chloride/hexane to yield (S)-2-(6-methoxy-2-naphthyl)propionic acid after recrystallization. |
Here is a chemical reaction formula: Reactants are:m2:Cl;m1:COC=1C=C2C=CC(=CC2=CC1)[C@@H](C(=O)O)C, Reagents are:m3:C(C(C)C)O, and Products are 0:COC=1C=C2C=CC(=CC2=CC1)[C@@H](C(=O)OCC(C)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 300 mg of (S)-2-(6-methoxy-2-naphthyl)propionic acid in 5 ml of isobutyl alcohol is saturated with hydrogen chloride. After 24 hours, the excess alcohol is distilled off in vacuo and the residue is purified by chromatography using an alumina substrate to yield isobutyl (S)-2-(6-methoxy-2-naphthyl)propionate. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m5_m4:C(CC(=O)C)(=O)OCC;m1_m2_m3_m5_m4:O=C(C)C=C(C)C;m1_m2_m3_m5_m4:CCCCCCC, Reagents are:m1_m2_m3_m5_m4:[Cl-].[Zn+2].[Cl-];m1_m2_m3_m5_m4:C1(=CC=CC=C1)C, and Products are 0:O=C1C=C(C(C(C1)(C)C)C(=O)OCC)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 1020 ml (1041 g, 8.00 mol) of ethyl acetoacetate, 960 ml (824 g, 8.40 mol) of mesityl oxide, 1000 ml of heptane, 600 ml of toluene, and 175 g of zinc chloride was heated at reflux in a 5000 ml round bottom flask while stirring. The flask was equipped with a Dean-Stark trap and drying tube. After 24 h, an additional 25 g of zinc chloride was added and refluxing continued for 36 h. After cooling, the reaction mixture was washed with 1500 ml of water, 5% sodium bicarbonate solution (2×1000 ml), and another 1500 ml of water. Removal of solvent by evaporation yielded 979 g of crude product. Distillation of the crude product provided 453.5 g of the desired ester which represents 27.0% yield. Distillation was at 124°-5° C. (3.0 torr). |
Here is a chemical reaction formula: Reactants are:m5_m1_m2_m3:CO;m5_m1_m2_m3:Cl;m5_m1_m2_m3:ClC1=CC=C(C=C1)\C(=C/C1=C(C=C(C=C1)Cl)Cl)\C(OC)OC, Reagents are:m5_m1_m2_m3:O;m4:O, and Products are 0:ClC1=CC=C(C=C1)/C(/C=O)=C\C1=C(C=C(C=C1)Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Thereafter, a mixture of 1,000 ml of distilled water, 500 ml of methanol, 50 ml (59.7 g; 0.62 mole) of concentrated hydrochloric acid and 350 g (0.98 mole) of (E)-2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3,3-dimethoxyprop-1-ene (I) is refluxed for 4 hours, while stirring. The mixture is cooled to room temperature and 1,000 ml of water are then added, while stirring. 300 g (0.96 mole; 98% of theory) of (E)-2-(4-chlorophenyl)-3-(2,4-dichlorophenyl)-acrolein are isolated in the form of pale yellowish crystals of melting point 106°-109° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(C=C[C@]4(C)[C@H]3CC[C@]12C)=O;m1_m2_m3:CS(=O)(=O)O;m1_m2_m3:C(C)(=O)OC(=C)C, Reagents are:m4:C1(=CC=CC=C1)C, and Products are 0:CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4CC(C=C[C@]4(C)[C@H]3CC[C@]12C)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 19 g (0.05 mol) of cholesta-1,4,6-trien-3-one (I), 4.8 g (0.05 mol) of methanesulfonic acid and 200 g (2 mol) of isopropenyl acetate were added 200 ml of toluene, and the resulting mixture was then heated under reflux for 6 hours. After completion of the reaction, the same treatment as in Example 1 was carried out to yield 11.7 g of cholesta-1,5,7-trien-3-ol (IV). The yield was 61%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(C=C[C@]4(C)[C@H]3CC[C@]12C)=O;m1_m2_m3:[K];m1_m2_m3:C(C)(=O)OC(=C)C, Reagents are:m4:C(C)(=O)OCCCC, and Products are 0:CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4CC(C=C[C@]4(C)[C@H]3CC[C@]12C)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 19 g (0.05 mol) of cholesta-1,4,6-trien-3-one (I), 6.8 g (0.05 mol) of potassium acid sulphate and 200 g (2 mol) of isopropenyl acetate were added 200 ml of butyl acetate, and the resulting mixture was heated under reflux for 7 hours. After completion of the reaction, the same treatment as in Example 1 was carried out to yield 11.1 g of cholesta-1,5,7-trien-3-ol (IV). The yield was 58%. |
Here is a chemical reaction formula: Reactants are:m1_m5_m2:ClC=1C=C2CCNC2=CC1;m1_m5_m2:[H-].[Na+];m3_m4:FC1=C(C(=O)N)C=CC=C1, Reagents are:m1_m5_m2:CS(=O)C;m3_m4:CS(=O)C, and Products are 0:ClC=1C=C2CCN(C2=CC1)C1=C(C(=O)N)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A slurry was prepared comprising 5-chloroindoline (15.3 gm, 0.1 mole), dimethylsulfoxide (DMSO) [50 ml] and sodium hydride (5.28 gm, 50% in oil, washed with hexane). The slurry was permitted to stir at room temperature for 1 hour. To this a solution of o-fluorobenzamide (15.2 gm, 1.1 eq.) in DMSO (20 ml) was added dropwise with the temperature between 17°-19° C. At the end of addition the reaction mixture was stirred at room temperature for 2 hours, then heated to 75°-78° C. for 16 hours. The reaction mixture was partitioned between methylene chloride (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with methylene chloride (150 ml). The combined organic solution was washed twice with water, twice with HCl (2N, 100 ml), brine (2×50 ml), dried over Na2SO4, concentrated to about 50 ml. Ether (50 ml) was added. The product was crystallized out upon standing overnight (about 16 hours). The yield was 14.2 gm (52%); m.p. 137°-138° C. Recrystallization from methylene chloride and ether yielded 2-(5-chloro-indolin-1-yl)benzamide (11.82 gm) m.p. 137°-138° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m7_m3:NC=1C=C(C=CC1F)N1CCC2=CC=CC=C12;m1_m2_m7_m3:C(C)N(CC)CC;m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl;m4_m5:C(C)N(CC)CC;m4_m5:C(=O)(Cl)Cl;m6_m9:C(\C=C/C(=O)O)(=O)O, Reagents are:m10:O;m8:C1(=CC=CC=C1)C;m1_m2_m7_m3:C(Cl)(Cl)Cl;m6_m9:C(C)O, and Products are 0:C(\C=C/C(=O)O)(=O)O.N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)F)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution under nitrogen, of 50.2 g (0.22 mole) of 1-(3-amino-4-fluorophenyl)indoline of Example 2b, and 66.7 g (0.66 mole) of triethylamine in 900 ml of chloroform was added 65.7 g (0.33 mole) of 4-methyl-1-piperazine carbonyl chloride hydrochloride in portions over 5 minutes. The reaction was refluxed for 6 hours when an additional 22.2 g (0.22 mole) of triethylamine and 43.8 g (0.22 mole) of the carbonyl chloride reagent were added. After refluxing overnight (about 16 hours) the reaction was cooled, treated with 1 liter of water and stirred vigorously for 15 minutes. The layers were separated, and the organic phase was washed twice with water, dried over Na2SO4, and concentrated in vacuo to leave 50 g. This material was dissolved in 150 ml of toluene and absorbed on a tall chromatography column containing 1.5 kg of silica gel made up in toluene. Elution first with toluene, then with increasing percentages (25% per step) of dichloromethane (CH2Cl2) in toluene, followed by 100% CH2Cl2, and finally by increasing percentages of methanol (1% per step) in CH2Cl2 brought forth 27.3 g (35% overall yield) of pure urea. 12.7 g (0.036 mole) was converted to the maleate salt in the following manner. The urea was dissolved in 30 ml of ethanol and treated with a solution of 4.64 g (0.04 mole) of maleic acid in 20 ml of warm ethanol. The salt crystals were collected, and found to weigh 13.2 g (78%). Two recrystallizations from ethanol furnished N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide maleate, m.p. 117°-120° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)F)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:FC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 10.6 g (0.030 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide of Example 2c in 250 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 500 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed thrice with water, dried over Na2SO4 and concentrated in vacuo to 9.1 g of an oil. This material was adsorbed on a tall chromatography column containing 400 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of pure tetracycle which were combined and concentrated to afford 3.5 g (35% overall yield) of product which crystallized. This was recrystallized from a small volume of acetone to furnish 2.1 g of 9-fluoro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 151°-153° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m7_m3:BrC1=CC(=C(C=C1)N1CCC2=CC=CC=C12)N;m1_m2_m7_m3:C([O-])([O-])=O.[K+].[K+];m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl;m6:C(\C=C/C(=O)O)(=O)O;m4_m5:C([O-])([O-])=O.[K+].[K+];m4_m5:C(=O)(Cl)Cl, Reagents are:m8:C(C)O;m1_m2_m7_m3:C(Cl)(Cl)Cl;m9:O, and Products are 0:C(\C=C/C(=O)O)(=O)O.BrC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution, under nitrogen of 43.5 g (0.15 mole) of 1-(4-bromo-2-aminophenyl)indoline of Example 3b and 82.8 g (0.60 mole) of milled potassium carbonate in 1000 ml of chloroform was added 44.7 g (0.225 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over 10 minutes. The reaction was refluxed for 6 hours when an additional charge of 10.4 g (0.075 mole) of potassium carbonate and 14.9 g (0.075 mole) of the carbonyl chloride reagent was added. After refluxing overnight (about 16 hours), the reaction was cooled, treated with 500 ml of water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed thrice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 200 ml of toluene and adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution first with toluene, then with increasing percentages of dichloromethane in toluene, (25% per step), followed by dichloromethane alone, and finally with 1% methanol in dichloromethane brought forth 24 g (overall 39% yield) of fairly pure urea. This was dissolved in 100 ml of ethanol and treated with a solution of 6.96 g (0.06 mole) of maleic acid dissolved in 50 ml of ethanol. The maleate salt was collected, dried, and found to weigh 17.3 g (22% overall), m.p. 175°-177° C. dec. Recrystallization from methanol (charcoal) afforded 12.7 g (16% overall yield) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate, m.p. 175°-177° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 9.14 g (0.022 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 3c in 250 ml of phosphorus oxychloride was refluxed for 7 hours under nitrogen then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 500 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed thrice with water, dried over Na2SO4 and concentrated in vacuo to 8.5 g (98%) of an oil. This material was adsorbed on a tall chromatography column containing 350 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of virtually pure tetracycle which were combined and concentrated to afford 4.6 g (53% overall yield) of product as a foam. This was crystallized from a small volume of methanol to furnish 2.6 g of 9-bromo-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 153°-155° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m3:N1CCC2=CC=CC=C12, Reagents are:m1_m2_m3:CN(C=O)C, and Products are 0:ClC1=CC(=C(C=C1)N1CCC2=CC=CC=C12)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 38.4 g (0.20 mole) of 1,4-dichloro-2-nitrobenzene and 59.6 g (0.50 mole) of indoline in 400 ml of dimethylformamide (DMF) was heated under nitrogen at 140°-145° C. overnight (23 hours). The DMF solvent was then removed in vacuo and the residue was dissolved in 500 ml of dichloromethane. This solution was extracted with H2O, with dilute hydrochloric acid, with brine, then dried over Na2SO4 and concentrated to an oil. This was adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution with toluene brought forth 22.1 g (40% overall yield) of product, which crystallized. A small portion was recrystallized from hexane to afford 1-(4-chloro-2-nitrophenyl)indoline, m.p. 97°-99° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:ClC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 6.30 g (0.017 mole) of N-[5-chloro-2-(2,3-dihydro-1H-indol-1-yl)-phenyl]-4-methyl-1piperazinecarboxamide of Example 4b in 100 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 250 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed four times with water, dried over Na2SO4 and concentrated in vacuo to 5.7 g (95%) of a semi-crystalline material. Recrystallization from acetone afforded 2.20 g (37% overall yield) of 9-chloro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 154°-156° C. |
Here is a chemical reaction formula: Reactants are:m4_m5:C(C)N(CC)CC;m4_m5:Cl.CN1CCN(CC1)C(=O)Cl;m6_m8:C(\C=C/C(=O)O)(=O)O;m1_m2_m7_m3:NC1=C(C=CC=C1)N1CCC2=CC=CC=C12;m1_m2_m7_m3:C(C)N(CC)CC;m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl, Reagents are:m6_m8:C(C)O;m1_m2_m7_m3:C(Cl)(Cl)Cl;m9:O, and Products are 0:C(\C=C/C(=O)O)(=O)O.N1(CCC2=CC=CC=C12)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution, under nitrogen, of 21.0 g (0.10 mole) of 1-(2-aminophenyl)indoline and 30.4 g (0.30 mole) of triethylamine in 400 ml of chloroform was added 29.9 g (0.15 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over about 5 minutes. The reaction was refluxed for 6 hours when an additional 10.1 g (0.10 mole) of triethylamine and 19.9 g (0.10 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride were added. After refluxing overnight (total of 25 hrs), the reaction was cooled, treated with 400 ml water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed twice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 100 ml of absolute ethanol and treated in one portion with a warm solution of 13.2 g (0.11 mole) of maleic acid in 50 ml of ethanol. After several hours, the crystals were collected, washed with ethanol, and dried to afford 19.2 g (43%), of product, m.p. 158° dec. An additional 4.5 g of pure salt was obtained from the mother liquor making the total amount of product 23.7 g and the yield 53%. 3.0 g of product were recrystallized from ethanol to provide 2.80 g of N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboximide maleate. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1(CCC2=CC=CC=C12)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:CN1CCN(CC1)C1=NC2=C(N3C4=C1C=CC=C4CC3)C=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 21.1 g (0.0627 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 7a was added 500 ml of phosphorus oxychloride and this was refluxed under nitrogen overnight. The excess POCl3 was then removed at aspirator pressure with warming. The residue was boiled and triturated on the steam bath with 60 ml of absolute ethanol until solution resulted. This solution was cooled and stirred resulting in separation of a solid. This solid was collected, washed with ethanol, with ether, and finally hexane, then dried to afford 19.0 g. This was partitioned between 200 ml of chloroform and 100 ml of water, with good stirring. Addition of 2.5N-NaOH rendered the medium basic, and the product base passed into the organic phase. This was separated, washed twice with water, dried over Na2SO4 and concentrated to 6.5 g of an oil. This oil was boiled with 60 ml of acetone, filtered from some insolubles, and the filtrate concentrated under nitrogen to 20 ml and allowed to crystallize. This gave 2.6 g of solid, m.p. 144°-146° C. dec. This material was treated with 20 ml of 2N-HCl with stirring. The resulting solution was filtered from a small amount of insolubles, then made basic with 2.5N-NaOH and the product extracted into dichloromethane. The latter extract was washed twice with water, dried over Na2SO4, and concentrated to an oil which began to crystallize. This was quickly dissolved in a small volume of boiling acetone and allowed to crystallize. The crystals were collected, washed with a little acetone, and dried to afford 2.00 g (10% overall yield) of 6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 149°-151° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:ClC=1C=C2CCNC2=CC1;m1_m2_m3_m4:ClC1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CN(C=O)C, and Products are 0:ClC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Cl)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 123 g (0.80 mole) of 5-chloroindoline, 134 g (0.70 mole) of 1,4-dichloronitrobenzene and 97 g (0.80 mole) of collidine in 1000 ml of dimethylformamide was heated under nitrogen at 150° C. for 48 hours. The mixture was then cooled, filtered from some insolubles, and the solvent was removed in vacuo with warming. The residue was partitioned between 1000 ml of dichloromethane and 500 ml of water. The water layer was removed and the organic phase was washed twice with 2N-hydrochloric acid, once with 2N-sodium hydroxide, once more with water, dried over Na2SO4 and concentrated to an oil weighing 230 g. This was dissolved in 170 ml of methanol and stirred at room temperature and then at 0° C. The resultant crystals were collected, washed well with cold methanol, and dried. This afforded 86.5 g (40% yield) of product, m.p. 130°-133° C. 4 g of 5-chloro-1-(4-chloro-2-nitrophenyl)indoline were recrystallized from methanol in 85% yield (overall yield: 34%); m.p. 133°-135° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4_m3:ClC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m4_m3:C1=CC=CC=C1, Reagents are:m1_m2_m4_m3:[Pt];m1_m2_m4_m3:C(C)O, and Products are 0:C(C)[O-].Cl.NC1=C(C=CC(=C1)Cl)N1CCC2=CC(=CC=C12)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A Parr bottle, charged with 12.4 g (0.040 mole) of 5-chloro-1-(4-chloro-2-nitrophenyl)indoline of Example 8a, 100 ml of benzene, 100 ml of absolute ethanol and 0.5 g of 1% Pt/C was shaken under an initial hydrogen pressure of 57 psig until uptake ceased. The catalyst was then removed by filtration and the filtrate was concentrated in vacuo to an oil weighing 11.2 g (100%). This was dissolved in 30 ml of ethanol and then 30 ml of ether saturated with hydrogen chloride was added. An additional 500 ml of plain ether was added, and the mixture was stirred at 0° C., to maximize precipitation. The hydrochloride salt was collected, dried, and found to weigh 9.2 g (73%), m.p. 174°-178° C. Recrystallization from ethanol (charcoal) afforded 1-(2-amino-4-chlorophenyl)-5-chloroindoline hydrochloride ethanolate in 58% overall yield, m.p. 177°-180° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCNC2=CC1;m1_m2:[H-].[Na+];m3_m4:FC1=C(C(=O)N)C=CC=C1, Reagents are:m3_m4:CS(=O)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C(=O)N)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A slurry was prepared from 5-bromoindoline (9.85 g, 50 mmoles) dimethylsulfoxide (DMSO) (35 ml), sodium hydride (2.6 g, 50% in oil, washed with hexane, 1.1 eq). The slurry was stirred for 30 minutes. To this a solution of o-fluorobenzamide (7.9 g, 1.1 eq) in DMSO (15 ml) was added dropwise with temperature between 12°-13° C. At the end of addition the reaction mixture was stirred at ambient temperature for 4 hours, then heated up to 55° C. for 24 hours. The reaction mixture was partitioned between dichloromethane (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with dichloromethane (DCM) (150 ml). The combined DCM solution was washed twice with water (100 ml), twice with 2N HCl (100 ml), twice with brine (50 ml), dried over Na2SO4 and concentrated to a solid. Purification was on a flash chromatographic column (150 gm of silica gel) eluted with dichloromethane (DCM) (3 l). This gave 6.4 g of product (40%). Recrystallization from a small amount of ether yielded the 2-(5-bromo-indolin-1-yl)benzamide, m.p. 120°-122° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC=C4)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of N-[2-(5-bromo-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide (11.5 g, 27.5 mmoles) and 750 ml of phosphorus oxychloride was stirred until a solution was obtained and then heated under reflux for 40 minutes. The reaction mixture was cooled. Excess phosphorus oxychloride was removed by evaporation at 50°-55° C. The residue was dried for 30 minutes under vacuum. Ice-chilled 2N sodium hydroxide solution (250 ml) and dichloromethane (350 ml) were added to the residue at 4° C. (ice-water bath). The mixture was stirred until all the solid had dissolved. The organic phase was separated and washed with brine (2 times, 200 ml), dried over anhydrous magnesium sulfate and concentrated. Crystallization from ether (100 ml) gave 5.7 g (57%) of product. Recrystallization from isopropanol yielded the analytical sample, mp 203°-204° C. |
Here is a chemical reaction formula: Reactants are:m3:[OH-].[Na+];m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1;m2:C1(=CC=CC=C1)N1CCNCC1, Reagents are:m1_m5:C1(=CC=CC=C1)C;m4:[Ti](Cl)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C2=CC=CC=C2)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 7.88 g (0.0250 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-one and 1200 ml of toluene was heated under nitrogen until a solution resulted. Then there was added 40.6 g (0.250 mole) of N-phenylpiperazine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for three hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated to an oil. The oil was taken up in 80 ml of hot methanol, from which the product crystallized, affording 7.8 g (68%) of product. Recrystallization from a hot solution of dichloromethane (25 ml), to which methanol (25 ml) was added, provided the analytical sample, mp 171°-173° C. |
Here is a chemical reaction formula: Reactants are:m2:C(CC)N1CCNCC1;m3:[OH-].[Na+];m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1, Reagents are:m4:[Ti](Cl)(Cl)(Cl)Cl;m1_m5:C1(=CC=CC=C1)C, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)CCC)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 7.88 g (0.0250 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated until a solution resulted. Then there was added 32.1 g (0.25 mole) of N-propylpiperazine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was refluxed for 3 hours, and then cooled to room temperature. The mixture was stirred with 500 ml of 2N sodium hydroxide solution for 15 minutes and the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, filtered, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated to an oily solid. The oily solid was dissolved in 25 ml of hot ethyl acetate, filtered, and allowed to crystallize first at room temperature, then at 0° C. to yield 3.20 g (30%) of product, mp 134°-136° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC=C4)N4CCN(CC4)C)C1, Reagents are:m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[O-2].[Mn+4], and Products are 0:ClC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC=C4)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-chloro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (6 g, 17 mmoles), in chloroform (150 ml) was added manganese dioxide (10.5 g). The mixture was heated under reflux for 24 hours. The mixture was cooled, filtered and the solid was washed with dichloromethane (200 ml). The filtrate was then concentrated to dryness. The residue was purified by flash chromatography over a silica gel column (150 g), eluted with 2% methanol in dichloromethane (4 l) and 3% methanol in dichloromethane (2 l). Evaporation of the eluent gave 3.8 g (63%) of product. Recrystallization from toluene (40 ml) yielded the analytical sample, mp 170°-172° C. |
Here is a chemical reaction formula: Reactants are:m2:CC1CCNCC1;m1_m4:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1, Reagents are:m3:[Ti](Cl)(Cl)(Cl)Cl;m1_m4:C1(=CC=CC=C1)C, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCC(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4.73 g (0.0150 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1000 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 14.9 g (0.150 mole) of 4-methylpiperidine, followed by 8.54 g (0.045 mole) of titanium tetrachloride. The mixture was refluxed for 3 hours, cooled to room temperature and filtered. The filtrate was stirred with 500 ml of 2N sodium hydroxide solution for 15 minutes and the layers were separated. The aqueous phase was extracted with 250 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to an oil which solidified. The solid was triturated twice with hexane to afford 4.9 g (83%) of product. Recrystallization from ethyl acetate provided the analytical sample, mp 177°-179° C. |
Here is a chemical reaction formula: Reactants are:m3:[OH-].[Na+];m2:N1CCSCC1;m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1, Reagents are:m4:[Ti](Cl)(Cl)(Cl)Cl;m1_m5:C1(=CC=CC=C1)C, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCSCC2)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 7.88 g (0.025 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 25.8 g (0.250 mole) of thiomorpholine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for 3 hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was crystallized from 100 ml of hot methanol to give 8.8 g (88%) of product. Recrystallization from a hot solution of dichloromethane (50 ml, charcoal) to which methanol (100 ml) was added provided the analytical sample, mp 165°-167° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=CC(=C(C1)NC(=O)N(C)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N(C)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 10.8 g (0.030 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-N',N'-dimethylurea and 110 ml of phosphorus oxychloride, under nitrogen, was heated under reflux for 6 hours, with stirring, and then cooled to room temperature. The excess phosphorus oxychloride was removed under vacuum with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and treated first with 250 ml of ice-cold 2N sodium hydroxide solution, and then with 500 ml of dichloromethane. The mixture was stirred and triturated until all the material passed into solution. The organic phase was separated, washed with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to an oil. The oil was dissolved in 50 ml of ethyl acetate and the solution was concentrated under a stream of nitrogen. At a volume of about 30 ml, the mixture was filtered. Concentration of the filtrate was continued to a volume of about 20 ml, during which crystallization resulted. The solid was dissolved by heating, the hot solution was filtered and allowed to crystallize to afford 4.9 g (48%) of product, mp 124°-127° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4_m3:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C(=O)O)C=CC=C1, Reagents are:m1_m2_m4_m3:Cl;m1_m2_m4_m3:[Pd];m1_m2_m4_m3:C(C)O, and Products are 0:CC=1C=C2C=3N(C4=C(C(N2)=O)C=CC=C4)CCC3C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 2-(5-methyl-7-nitroindolin-1-yl)benzoic acid (9 g, 0.03 mole), conc. hydrochloric acid (several drops) and ethanol (200 ml) was added 5% palladium-charcoal (1.5 gm). The mixture was shaked under hydrogen (58 psi) for 30 hours. The solvent was removed and the residue was loaded onto a silica gel flash chromatography column (800 g, 230-400 mesh), packed and eluted with dichloromethane (4 l) and 2% methanol in dichloromethane (4 l). The fractions containing product were pooled and evaporated to yield 5 g (66%) of product. Recrystallization from chloroform gave the analytical sample, mp 222°-224° C. |
Here is a chemical reaction formula: Reactants are:m6_m7:C([O-])(O)=O.[Na+];m6_m7:CN(C(=O)Cl)C;m4_m5:C([O-])(O)=O.[Na+];m4_m5:CN(C(=O)Cl)C;m8:O;m1_m2_m9_m3_m10:Cl.NC1=C(C=CC(=C1)Br)N1CCC2=CC=CC=C12;m1_m2_m9_m3_m10:C([O-])(O)=O.[Na+];m1_m2_m9_m3_m10:CN(C(=O)Cl)C, Reagents are:m1_m2_m9_m3_m10:C(Cl)(Cl)Cl;m1_m2_m9_m3_m10:C(Cl)(Cl)Cl, and Products are 0:BrC=1C=CC(=C(C1)NC(=O)N(C)C)N1CCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred mixture, under nitrogen, of 28.9 g (0.10 mole) of 1-(2-amino-4-bromophenyl)indoline hydrochloride and 16.8 g (0.20 mole) of anhydrous powdered sodium bicarbonate in 500 ml of chloroform was added a solution of 21.5 g (0.20 mole) of dimethylcarbamyl chloride in 25 ml of chloroform, over a 10 minute period. The mixture was heated under reflux for 7 hours, and 8.4 g (0.10 mole) of sodium bicarbonate and 10.7 g (0.10 mole) of the dimethylcarbamyl chloride were added. After heating under reflux for 2 days, equivalent amounts (8.4 g of sodium bicarbonate and 10.7 g of dimethylcarbamyl chloride) were added. After three days under reflux, the mixture was cooled and 500 ml of water was added. The phases were stirred vigorously for 0.5 hours and separated. The organic phase was washed three times with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in 200 ml of dichloromethane and adsorbed on a chromatography column containing 1 kg of silica gel packed in and eluted with dichloromethane. The fractions containing product were combined and concentrated to afford 14.5 g (40%) of product. Recrystallization from toluene (charcoal)/hexane gave the analytical sample, mp 119°-121° C. |
Here is a chemical reaction formula: Reactants are:m4:ClCCl;m1_m2_m3_m5:BrC=1C=C2CCNC2=CC1;m1_m2_m3_m5:N1=C(C=C(C=C1C)C)C;m1_m2_m3_m5:FC1=C(C=CC=C1)[N+](=O)[O-], Reagents are:m1_m2_m3_m5:C=1(C(=CC=CC1)C)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-Bromoindoline (4.0 g, 0.02 mole), collidine (3.6 g, 0.03 mole), and o-fluoronitrobenzene (2.8 g, 0.02 mole) in xylene (25 ml) were heated at 185° C. (oil bath temperature) for 24 hours. The mixture was cooled to room temperature and poured into dichloromethane. The dichloromethane solution was washed with 1N hydrochloric acid (3 times, 150 ml), brine (200 ml), dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated. Crystallization of the residue was induced by stirring in ether (15 ml) followed by hexane (200 ml), then chilling in the refrigerator overnight. The solid was filtered and washed with hexane and dried to yield 3.5 g (55%) of product. Recrystallization from 2-propanol yielded the analytical sample, mp 12°-114° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m5:[OH-].[K+];m1_m4_m5:C(CO)O;m2:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C#N)C=CC=C1;m3_m6:ClCCl, Reagents are:m1_m4_m5:O;m3_m6:O, and Products are 0:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C(=O)O)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution under nitrogen of potassium hydroxide (30 g, 0.53 mole) in ethylene glycol (250 ml) and water (35 ml) was heated to 175° C., at which temperature there was added 2-(5-methyl-7-nitroindolin-1-yl)benzonitrile (26 g, 0.093 mole). After heating at 175° C. for 3 hours, the reaction mixture was cooled to room temperature and dichloromethane (1 liter) and water (500 ml), were added, with stirring. The aqueous phase was separated and extracted with two 250 ml-portions of dichloromethane. The aqueous phase was then cooled in an ice-bath and acidified with concentrated hydrochloric acid. The product was extracted out with three 500 ml-portions of dichloromethane. The combined organic extracts were washed twice with brine, dried, filtered, and concentrated to afford 9.0 g (32%) of product. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)N(C([O-])=O)C1=CC=CC=C1;m1_m2_m3:CN1CCNCC1, Reagents are:m1_m2_m3:CCOCC, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)phenyl]phenylcarbamate (11.5 g, 28.5 mmoles), N-methylpiperazine (15 ml) and ether (50 ml) was stirred at room temperature for 2 hours. The ether was evaporated. The mixture was filtered through a silica gel column (150 g), packed with dichloromethaane, and the column was washed with 2% methanol-dichloromethane solution (2 l). The solvent was evaporated. The residue was purified by flash chromatography on a silica gel column (150 g, 230-400 mesh), eluted with 1% methanol/dichloromethane (4 l), 1.5% methanol/dichloromethane (2 l), and 2% methanol/dichloromethane. The fractions containing the desired material were collected and evaporated to give 10.9 g (90%) of product. Crystallization from chloroform and hexane afforded the analytical sample, mp 108°-110° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:FC1=C(C=CC=C1)[N+](=O)[O-];m1_m2_m3_m4:N1CCCC2=CC=CC=C12;m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CC1=C(C(=CC=C1)C)C, and Products are 0:[N+](=O)([O-])C1=C(C=CC=C1)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture, under nitrogen of 70.6 g (0.50 mole) of 1-fluoro-2-nitrobenzene, 133.2 g (1.00 mole) of 1,2,3,4-tetrahydroquinoline and 121.2 g (1.00 mole) of symmetrical collidine in 500 ml of 1,2,3-trimethylbenzene was refluxed (bp 178°) for 5 days. The mixture was concentrated in vacuo. The residue was taken up in 1000 ml of chloroform and extracted with 500 ml of 2N-hydrochloric acid. The aqueous phase was back extracted with 250 ml of chloroform. The combined organic layers were washed 3 times with 2N-hydrochloric acid, once with 2N-sodium hydroxide solution, twice with water and dried over anhydrous sodium sulfate. The solvent was removed in vacuo. The residual oil was dissolved in 300 ml of 1:1 hexane:toluene and adsorbed on a chromatography column containing 2 kg of silica gel packed in hexane. Elution with 1:1 hexane:toluene gave fractions containing product. The fractions were combined and concentrated to afford 28.2 g (22%) of product. Recrystallization from hot isopropyl ether afforded the analytical sample, mp 69°-71° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)C)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)C)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide (3.3 g, 7.68 mmoles) and phosphorus oxychloride (30 ml) was heated at reflux for 25 minutes under nitrogen. The solution was cooled and excess phosphorus oxychloride was removed at 55°-60° C. under vacuum. Ice-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml) were added to the residue. The organic phase was separated and washed with brine (2 times, 100 ml), dried over anhydrous magnesium sulfate, and concentrated. Purification was accomplished by flash chromatography over aluminum oxide (Grade III, 100 g), eluted with dichloromethane (2 l). The fractions containing pure material were pooled and concentrated. Recrystallization from isopropanol (30 ml) yielded 1.7 g (53.9%) of product, mp 187°-189° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:BrN1C(CCC1=O)=O;m1_m4_m2_m5:CN1CCN(CC1)C1=NC2=C(N3C4=C1C=CC=C4CC3)C=CC(=C2)C;m3:ClCCl, Reagents are:m1_m4_m2_m5:CN(C=O)C;m1_m4_m2_m5:CN(C=O)C, and Products are 0:BrC=1C(=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-bromosuccinimide (0.91 g, 5.1 mmoles) in dimethylformamide (3 ml) was added dropwise to a solution of 6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (1.6 g, 4.8 mmoles) in dimethylformamide (30 ml) at 0°-3° C. The reaction mixture was stirred for 30 minutes. The solution was poured into dichloromethane (250 ml), and was washed with brine (4 times, 150 ml), and dried over anhydrous magnesium sulfate. The solvent was removed at reduced pressure and the residue was dried. Purification was accomplished by flash chromatography on an aluminium oxide column (grade III, 60 g), eluted with dichloromethane (500 ml) and 2% methanol in dichloromethane (250 ml). The fractions containing the product were pooled and concentrated. Recrystallization from 2-propanol:water (1:1, 20 ml) yielded 230 mg (11.6%) of product, mp 177°-177° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)C)N4CCN(CC4)C)C1, Reagents are:m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[O-2].[Mn+4], and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC(=C4)C)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-bromo-6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (5.7 g, 13.8 mmoles) in chloroform (540 ml) was added manganese dioxide (25 gm), and the mixture was heated under reflux for 4 days. The mixture was filtered, and the filter cake washed with dichloromethane. The filtrate was concentrated under vacuum. The residue was purified on a silica gel column, eluted with 2% methanol/dichloromethane. The fractions (75-100 ml each) containing pure product were pooled and concentrated. Recrystallization from a small volume of 2-propanol yielded 2.41 g (42%) of product, mp 153°-155° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)C)[N+](=O)[O-];m1_m2_m3_m4:ClCCl, Reagents are:m1_m2_m3_m4:C(C)O;m1_m2_m3_m4:[Pt], and Products are 0:Cl.NC1=C(C=CC(=C1)C)N1CCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a warm solution of 4-(5-bromo-1-indolinyl)-3-nitrotoluene (10 g, 0.03 mole) in dichloromethane (40 ml) and ethanol (160 ml) was added 1% platinum-on-carbon (2.0 gm). The mixture was shaken under hydrogen (57 psi) for 3.5 hours. The mixture was filtered and concentrated. The residue was dried under vacuum at 55° C. Purification was accomplished by flash chromatography over silica gel (100 g), eluted with a mixture of hexane:dichloromethane (3:1, 2 l and 1:1, 1 l). The fractions containing pure product were pooled and concentrated. The residue was dissolved in ether (250 ml) and added to a methanol/hydrogen chloride solution, and the mixture was stirred at 0° C. for 10 minutes. The precipitate was filtered and dried to afford 4.0 g (39%) of product, mp 195°-200° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:[N+](=O)([O-])C1=C(C=CC(=C1)Br)N1CCC2=CC=CC=C12;m1_m4_m2_m5:BrN1C(CCC1=O)=O;m3:O, Reagents are:m1_m4_m2_m5:CN(C=O)C;m1_m4_m2_m5:CN(C=O)C, and Products are 0:[N+](=O)([O-])C1=C(C=CC(=C1)Br)N1CCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 1-(2-nitro-4-bromophenyl)indoline (15 g, 0.047 moles) in dimethylformamide (150 ml) at -10° C. was added dropwise a solution of N-bromosuccinimide (9.4 g, 0.054 mole) in dimethylformamide (50 ml) over 10 minutes. The reaction mixture was stirred at 0° C. for 15 minutes. The solution was added slowly to water (1 l) with vigorous stirring. The solid was filtered, dried, and dissolved in dichloromethane (300 ml). The solution was added to boiling methanol (1 l). The precipitate was collected by filtration to give 12.7 g (68%) of product, mp 150°-152° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:BrN1C(CCC1=O)=O;m1_m2_m4:N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C;m3:ClCCl, Reagents are:m1_m2_m4:CN(C=O)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-Bromosuccinimide (2.6 g, 14.5 mmoles) was added to a solution of N-[2-(indolin-1-yl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide (5.0 g, 12.0 mmoles) in dimethylformamide (50 ml). The solution was stirred at room temperature for 15 minutes and at 60° C. for 15 minutes. The solution was cooled and poured into dichloromethane (500 ml). The layers were separated and the organic phase was washed with water (3×500 ml), brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was concentrated. The residue was purified by chromatography over silica gel (60 g, eluted with 4% methanol:96% dichloromethane, 1 l). The appropriate fractions were pooled and concentrated to give 4.8 g (84%) of product. Recrystallization from chloroform and hexane gave the analytical sample, mp 118°-119.5° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)Br)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide (12.3 g, 24.8 mmoles) and phosphorus oxychloride (250 ml) was heated under reflux for 1 hour. The reaction mixture was cooled and then concentrated at 50°-60° C. under vacuum. Ice-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml) was added to the reaction mixture. The mixture was stirred for 20 minutes. The organic phase was separated and the aqueous phase was extracted once with dichloromethane (250 ml). The combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml), dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The residue was purified on a silica gel column (250 gm), eluted with 2% and then 3% methanol:dichloromethane. The appropriate fractions were combined and concentrated to give 8.3 g (70%) of product. Recrystallization from isopropanol gave the analytical sample, mp 215°-216° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)Br)N4CCN(CC4)C)C1, Reagents are:m4:[O-2].[O-2].[Mn+4];m1_m3_m2:C(Cl)(Cl)Cl;m1_m3_m2:[O-2].[O-2].[Mn+4], and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC(=C4)Br)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture 4,9-dibromo-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]-benzodiazepine (4.5 g, 9.45 mmoles) and manganese(IV) dioxide (7.0 g) in chloroform (150 ml) was heated under reflux for 3.5 hours. An additional 4.5 g of manganese dioxide was added. The reaction mixture was stirred overnight at room temperature. The mixture was filtered through celite and the filtrate was concentrated. The residue was purified by flash chromatography over a silica gel column (140 gm), eluted with 2% methanol:98% dichloromethane (2 l). The appropriate fractions were collected and evaporated. Crystallization of the residue from isopropanol (10 ml) yielded 3.37 g (75%) of product, mp 158°-159° C. |
Here is a chemical reaction formula: Reactants are:m3:[OH-].[Na+];m2_m5:BrN1C(CCC1=O)=O;m1_m4:[N+](=O)([O-])C1=C(C=CC=C1)N1CCCC2=CC=CC=C12, Reagents are:m2_m5:CN(C=O)C;m1_m4:CN(C=O)C, and Products are 0:BrC=1C=C2CCCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen, of 1-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (76.3 g, 0.30 mole) in dimethylformamide (1000 ml) was cooled to -10° C. A solution of of N-bromosuccinimide (58.7 g, 0.33 mole) in dimethylformamide (250 ml) was added dropwise at such a rate as to keep the reaction temperature below 0° C. (1.5 hours). Half-an hour after the addition was completed, the reaction mixture was poured into 7 liters of 2N-sodium hydroxide solution/ice, with stirring. The product separated as an oil. The quench fluids were decanted and the oil was rinsed several times with water. The oil was dissolved in dichloromethane (1.5 l). The organic solution was extracted once with 2N-sodium hydroxide solution, thrice with water, dried over sodium sulfate and concentrated. The residue was dissolved in 1:1 hexane:toluene (250 ml) and the solution was absorbed on a chromatography column containing 2 kg of silica gel packed in 1:1 hexane:toluene. Elution with this solvent mixture provided 82.7 g (82%) of product, as an oil. For analysis, a sample was Kugelrohr distilled at a vessel temperature of 166°-168° C. (0.2 mm Hg). |
Here is a chemical reaction formula: Reactants are:m1_m6_m2_m3:BrC=1C=C2CCCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-];m1_m6_m2_m3:C1=CC=CC=C1;m1_m6_m2_m3:C(C)O;m4_m5:C(\C=C/C(=O)O)(=O)O, Reagents are:m1_m6_m2_m3:[Pt];m4_m5:CCOCC, and Products are 0:C(\C=C/C(=O)O)(=O)O.NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A Parr hydrogenation bottle was charged with 6-bromo-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (16.7 g, 0.050 mole), 1% platinum-on-carbon (1 g), benzene (100 ml) and ethanol (100 ml). The mixture was shaken under an initial hydrogen pressure of 58 psi until uptake ceased. The mixture was then filtered to remove the catalyst and the filtrate was concentrated under vacuum. The residue was taken up in hot ether (150 ml), filtered, and the filtrate was treated with a hot solution of maleic acid (6.4 g, 0.055 mole) in ether (500 ml). The solution was boiled down to about 300 ml and allowed to cool. The supernatant was decanted from an oil, which separated. The supernatant was concentrated and the process was repeated several times to give 11.4 g (55%) of product. Recrystallization from ethyl acetate afforded the analytical sample, mp 113°-116° C. |
Here is a chemical reaction formula: Reactants are:m6_m10:C(\C=C/C(=O)O)(=O)O;m4_m8:CN1CCNCC1;m5:CN1CCNCC1;m3:C1(=CC=CC=C1)OC(=O)Cl;m1_m2_m7:NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br;m1_m2_m7:C(C)N(CC)CC, Reagents are:m6_m10:C(C)O;m4_m8:ClCCl;m11:O;m9:ClCCl;m1_m2_m7:ClCCl, and Products are 0:C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen, of 1-(2-aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline (21.2 g, 0.070 mole) and triethylamine (10.1 g, 0.10 mole) in dichloromethane (200 ml) was cooled to 0° C. Then there was added dropwise phenylchloroformate (15.7 g, 0.10 mole) at such a rate as to keep the reaction temperature below 5° C. The addition took 30 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 2 hours at room temperature, and N-methylpiperazine (28.1 g, 0.28 mole) dissolved in dichloromethane (30 ml) was added dropwise over a 45 minute period. The solution was stirred for 3 hours and an additional charge of N-methylpiperazine (14.05 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added, and the mixture was stirred overnight. Water (250 ml) was added with vigorous stirring. The layers were separated and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in ethanol (200 ml), with heating, and treated with a warm solution of maleic acid (8.93 g, 0.077 mole) in ethanol (100 ml). The maleate salt was collected to give 23.2 g (61%) of product. Recrystallization from methanol afforded the analytical sample, mp 172°-174° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2CCCN3C2=C(C(=NC2=C3C=CC=C2)N2CCN(CC2)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 4-methyl-N-[2-(6-bromo-1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazine-carboxamide (14.2 g, 0.0330 mole) in phosphorus oxychloride (250 ml) was heated under reflux under nitrogen for 5 hours. The reaction mixture was cooled to room temperature and excess phosphorous oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (500 ml). The mixture was stirred, the organic phase was separated, washed with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was digested in boiling methanol (40 ml) to afford 10.7 g (79%) of product. Recrystallization from ethanol provided the analytical sample, mp 181°-183° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:BrC1=C(C=C(C=C1)Br)[N+](=O)[O-];m1_m2_m3_m4:N1CCCC2=CC=CC=C12;m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CC1=C(C(=CC=C1)C)C, and Products are 0:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture, under nitrogen, of 2,5-dibromonitrobenzene (140.5 g, 0.50 mole), 1,2,3,4-tetrahydroquinoline (133.2 g, 1.00 mole) and symmetrical collidine (121.2 g, 1.00 mole) in 1,2,3-trimethylbenzene (500 ml) as solvent was heated at 160°-165° C. for 7 days. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated in vacuo (100° C.). The residue was taken up in dichloromethane (1.5 l) and the solution was extracted three times with dilute hydrochloric acid, once with dilute sodium hydroxide solution, three times with water, dried over anhydrous sodium sulfate and concentrated. This residue was dissolved in 1:1 hexane:toluene (250 ml) and adsorbed on a chromatography column containing 3 kg of silica gel. Elution with 1:1 hexane:toluene gave 30 g (18%) of product, as an oil. A portion of the oil was Kugelrohr distilled at an oven-temperature of 163°-165° C. (0.1 mm Hg) to provide the analytical sample. |
Here is a chemical reaction formula: Reactants are:m2:C(C)O;m1_m3:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)[N+](=O)[O-], Reagents are:m4:[Pt];m1_m3:C1=CC=CC=C1, and Products are 0:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-(4-Bromo-2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (11.6 g, 0.035 mole) was dissolved in benzene (125 ml), and ethanol added (75 ml), followed by 1% platinum-on-charcoal (0.40 g). The mixture was shaken under an initial pressure of 56 psi for 6.5 hours. The mixture was filtered and the filtrate was evaporated at 50° C. under vacuum to provide 10.6 g (100%) of product, as a gum. |
Here is a chemical reaction formula: Reactants are:m1_m6:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)N;m3:C1(=CC=CC=C1)OC(=O)Cl;m5_m9:CN1CCNCC1;m2:C(C)N(CC)CC;m4:C1(=CC=CC=C1)OC(=O)Cl, Reagents are:m10:O;m8:ClCCl;m1_m6:ClCCl;m5_m9:ClCCl, and Products are 0:CN1CCN(CC1)C(=O)NC1=C(C=CC(=C1)Br)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-(4-Bromo-2-aminophenyl)-1,2,3,4-tetrahydroquinoline (10.6 g, 0.035 mole) was dissolved on a steam bath in dichloromethane (150 ml). The solution was cooled to -5° C. in ice/methanol and triethylamine (5.01 g, 0.050 mole) was added in one portion, followed by a solution of phenylchloroformate (7.85 g, 0.050 mole) dissolved in dichloromethane (10 ml), dropwise over 15 minutes. The mixture was stirred 1 hour in the cold, 2 hours at room temperature, and an additional charge of phenylchloroformate (1.57 g, 0.010 mole) was added. After one hour, a solution of N-methylpiperazine (14.1 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added over 0.5 hour. The reaction mixture was stirred under nitrogen at room temperature overnight. Water (100 ml) was added and the mixture was stirred 0.5 hour. The organic phase was separated, washed 4 times with water, dried over anhydrous sodium sulfate, and evaporated in a 100° C. bath in vacuo. The residue was dissolved in toluene (40 ml), adsorbed on a column of silica gel (500 g) packed in toluene and eluted with dichloromethane-methanol (98:2). The appropriate fractions were combined and evaporated to give 9.2 g (61%) of product, as an oil. |
Here is a chemical reaction formula: Reactants are:m1_m2:CN1CCN(CC1)C(=O)NC1=C(C=CC(=C1)Br)N1CCCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=CC2=C(N=C(C3=C4N2CCCC4=CC=C3)N3CCN(CC3)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide (8.6 g, 0.020 mole) in phosphorus oxychloride (200 ml) was heated under reflux under nitrogen for 6 hours. The reaction mixture was cooled to room temperature and excess phosphorus oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml). The mixture was stirred and triturated until the residue dissolved. The organic phase was separated, washed again with 2N sodium hydroxide solution, twice with water, dried over sodium sulfate, and concentrated in vacuo. The residue was taken up in 4N hydrochloric acid (100 ml), filtered, and the filrate was stirred 15 minutes with charcoal. After filtration, the solution was stirred with dichloromethane (100 ml), and the mixture was made alkaline by the addition of cold 2N sodium hydroxide solution. The organic phase was separated, washed twice with water, dried over sodium sulfate, and boiled 15 minutes with charcoal. After filtration, the solution was concentrated to give 4.6 g (56%) of product, as an oil, which crystallized on standing. The product was taken up in boiling methanol (20 ml) and allowed to crystallize first at room temperature, then in the refrigerator. Recrystallization from methanol afforded the analytical sample, mp 153°-156° C. |
Here is a chemical reaction formula: Reactants are:m6_m8:C(\C=C/C(=O)O)(=O)O;m5:CN1CCNCC1;m1_m2_m7:NC1=C(C=CC=C1)N1CCCC2=CC=CC=C12;m1_m2_m7:C(C)N(CC)CC;m4:CN1CCNCC1;m3:C1(=CC=CC=C1)OC(=O)Cl, Reagents are:m9:O;m6_m8:C(C)O;m1_m2_m7:ClCCl, and Products are 0:C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen of 1-(2-aminophenyl)-1,2,3,4-tetrahydroquinoline (4.50 g, 0.020 mole), and triethylamine (3.04 g, 0.030 mole) in dichloromethane (50 ml) was cooled to 0° C. and phenylchloroformate (4.70 g, 0.030 mole) was added dropwise at such a rate such as to keep the reaction temperature below 5° C. The addition took 10 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 1 hour at room temperature, and N-methylpiperazine (8.02 g, 0.080 mole) was added dropwise over a 5 minute period. The solution was stirred for 2 hours, N-methyl-piperazine (4.01 g, 0.040 mole) was added and the solution was stirred overnight. Water (100 ml) was added with vigorous stirring. The layers were separated, and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in ethanol (100 ml) and treated with a warm solution of maleic acid (2.6 g 0.022 mole) in ethanol (15 ml). The precipitate was collected to provide 6.1 g (65%) of product. Recrystallization from methanol afforded the analytical sample, mp 171°-173° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m5_m2:ClC=1C=C2CCNC2=CC1;m1_m5_m2:[H-].[Na+];m3_m4:FC1=C(C(=O)N)C=CC=C1, Reagents are:m1_m5_m2:CS(=O)C;m3_m4:CS(=O)C, and Products are 0:ClC=1C=C2CCN(C2=CC1)C1=C(C(=O)N)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A slurry was prepared comprising 5-chloroindoline (15.3 gm, 0.1 mole), dimethylsulfoxide (DMSO) [50 ml] and sodium hydride (5.28 gm, 50% in oil, washed with hexane). The slurry was permitted to stir at room temperature for 1 hour. To this a solution of o-fluorobenzamide (15.2 gm, 1.1 eq.) in DMSO (20 ml) was added dropwise with the temperature between 17°-19° C. At the end of addition the reaction mixture was stirred at room temperature for 2 hours, then heated to 75°-78° C. for 16 hours. The reaction mixture was partitioned between methylene chloride (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with methylene chloride (150 ml). The combined organic solution was washed twice with water, twice with HCl (2N, 100 ml), brine (2×50 ml), dried over Na2SO4, concentrated to about 50 ml. Ether (50 ml) was added. The product was crystallized out upon standing overnight (about 16 hours). The yield was 14.2 gm (52%); m.p. 137°-138° C. Recrystallization from methylene chloride and ether yielded 2-(5-chloro-indolin-1-yl)benzamide (11.82 gm) m.p. 137°-138° C. |
Here is a chemical reaction formula: Reactants are:m4_m5:C(C)N(CC)CC;m4_m5:C(=O)(Cl)Cl;m1_m2_m7_m3:NC=1C=C(C=CC1F)N1CCC2=CC=CC=C12;m1_m2_m7_m3:C(C)N(CC)CC;m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl;m6_m9:C(\C=C/C(=O)O)(=O)O, Reagents are:m1_m2_m7_m3:C(Cl)(Cl)Cl;m10:O;m6_m9:C(C)O;m8:C1(=CC=CC=C1)C, and Products are 0:C(\C=C/C(=O)O)(=O)O.N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)F)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution under nitrogen, of 50.2 g (0.22 mole) of 1-(3-amino-4-fluorophenyl)indoline of Example 2b, and 66.7 g (0.66 mole) of triethylamine in 900 ml of chloroform was added 65.7 g (0.33 mole) of 4-methyl-1-piperazine carbonyl chloride hydrochloride in portions over 5 minutes. The reaction was refluxed for 6 hours when an additional 22.2 g (0.22 mole) of triethylamine and 43.8 g (0.22 mole) of the carbonyl chloride reagent were added. After refluxing overnight (about 16 hours) the reaction was cooled, treated with 1 liter of water and stirred vigorously for 15 minutes. The layers were separated, and the organic phase was washed twice with water, dried over Na2SO4, and concentrated in vacuo to leave 50 g. This material was dissolved in 150 ml of toluene and absorbed on a tall chromatography column containing 1.5 kg of silica gel made up in toluene. Elution first with toluene, then with increasing percentages (25% per step) of dichloromethane (CH2Cl2) in toluene, followed by 100% CH2Cl2, and finally by increasing percentages of methanol (1% per step) in CH2Cl2 brought forth 27.3 g (35% overall yield) of pure urea. 12.7 g (0.036 mole) was converted to the maleate salt in the following manner. The urea was dissolved in 30 ml of ethanol and treated with a solution of 4.64 g (0.04 mole) of maleic acid in 20 ml of warm ethanol. The salt crystals were collected, and found to weigh 13.2 g (78%). Two recrystallizations from ethanol furnished N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide maleate, m.p. 117°-120° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)F)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:FC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 10.6 g (0.030 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide of Example 2c in 250 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 500 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed thrice with water, dried over Na2SO4 and concentrated in vacuo to 9.1 g of an oil. This material was adsorbed on a tall chromatography column containing 400 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of pure tetracycle which were combined and concentrated to afford 3.5 g (35% overall yield) of product which crystallized. This was recrystallized from a small volume of acetone to furnish 2.1 g of 9-fluoro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 151°-153° C. |
Here is a chemical reaction formula: Reactants are:m4_m5:C([O-])([O-])=O.[K+].[K+];m4_m5:C(=O)(Cl)Cl;m6:C(\C=C/C(=O)O)(=O)O;m1_m2_m7_m3:BrC1=CC(=C(C=C1)N1CCC2=CC=CC=C12)N;m1_m2_m7_m3:C([O-])([O-])=O.[K+].[K+];m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl, Reagents are:m1_m2_m7_m3:C(Cl)(Cl)Cl;m8:C(C)O;m9:O, and Products are 0:C(\C=C/C(=O)O)(=O)O.BrC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution, under nitrogen of 43.5 g (0.15 mole) of 1-(4-bromo-2-aminophenyl)indoline of Example 3b and 82.8 g (0.60 mole) of milled potassium carbonate in 1000 ml of chloroform was added 44.7 g (0.225 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over 10 minutes. The reaction was refluxed for 6 hours when an additional charge of 10.4 g (0.075 mole) of potassium carbonate and 14.9 g (0.075 mole) of the carbonyl chloride reagent was added. After refluxing overnight (about 16 hours), the reaction was cooled, treated with 500 ml of water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed thrice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 200 ml of toluene and adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution first with toluene, then with increasing percentages of dichloromethane in toluene, (25% per step), followed by dichloromethane alone, and finally with 1% methanol in dichloromethane brought forth 24 g (overall 39% yield) of fairly pure urea. This was dissolved in 100 ml of ethanol and treated with a solution of 6.96 g (0.06 mole) of maleic acid dissolved in 50 ml of ethanol. The maleate salt was collected, dried, and found to weigh 17.3 g (22% overall), m.p. 175°-177° C. dec. Recrystallization from methanol (charcoal) afforded 12.7 g (16% overall yield) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate, m.p. 175°-177° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 9.14 g (0.022 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 3c in 250 ml of phosphorus oxychloride was refluxed for 7 hours under nitrogen then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 500 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed thrice with water, dried over Na2SO4 and concentrated in vacuo to 8.5 g (98%) of an oil. This material was adsorbed on a tall chromatography column containing 350 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of virtually pure tetracycle which were combined and concentrated to afford 4.6 g (53% overall yield) of product as a foam. This was crystallized from a small volume of methanol to furnish 2.6 g of 9-bromo-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 153°-155° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m3:N1CCC2=CC=CC=C12, Reagents are:m1_m2_m3:CN(C=O)C, and Products are 0:ClC1=CC(=C(C=C1)N1CCC2=CC=CC=C12)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 38.4 g (0.20 mole) of 1,4-dichloro-2-nitrobenzene and 59.6 g (0.50 mole) of indoline in 400 ml of dimethylformamide (DMF) was heated under nitrogen at 140°-145° C. overnight (23 hours). The DMF solvent was then removed in vacuo and the residue was dissolved in 500 ml of dichloromethane. This solution was extracted with H2O, with dilute hydrochloric acid, with brine, then dried over Na2SO4 and concentrated to an oil. This was adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution with toluene brought forth 22.1 g (40% overall yield) of product, which crystallized. A small portion was recrystallized from hexane to afford 1-(4-chloro-2-nitrophenyl)indoline, m.p. 97°-99° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC=1C=CC(=C(C1)NC(=O)N1CCN(CC1)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:ClC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 6.30 g (0.017 mole) of N-[5-chloro-2-(2,3-dihydro-1H-indol-1-yl)-phenyl]-4-methyl-1piperazinecarboxamide of Example 4b in 100 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 250 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed four times with water, dried over Na2SO4 and concentrated in vacuo to 5.7 g (95%) of a semi-crystalline material. Recrystallization from acetone afforded 2.20 g (37% overall yield) of 9-chloro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 154°-156° C. |
Here is a chemical reaction formula: Reactants are:m4_m5:C(C)N(CC)CC;m4_m5:Cl.CN1CCN(CC1)C(=O)Cl;m1_m2_m7_m3:NC1=C(C=CC=C1)N1CCC2=CC=CC=C12;m1_m2_m7_m3:C(C)N(CC)CC;m1_m2_m7_m3:Cl.CN1CCN(CC1)C(=O)Cl;m6_m8:C(\C=C/C(=O)O)(=O)O, Reagents are:m9:O;m1_m2_m7_m3:C(Cl)(Cl)Cl;m6_m8:C(C)O, and Products are 0:C(\C=C/C(=O)O)(=O)O.N1(CCC2=CC=CC=C12)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution, under nitrogen, of 21.0 g (0.10 mole) of 1-(2-aminophenyl)indoline and 30.4 g (0.30 mole) of triethylamine in 400 ml of chloroform was added 29.9 g (0.15 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over about 5 minutes. The reaction was refluxed for 6 hours when an additional 10.1 g (0.10 mole) of triethylamine and 19.9 g (0.10 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride were added. After refluxing overnight (total of 25 hrs), the reaction was cooled, treated with 400 ml water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed twice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 100 ml of absolute ethanol and treated in one portion with a warm solution of 13.2 g (0.11 mole) of maleic acid in 50 ml of ethanol. After several hours, the crystals were collected, washed with ethanol, and dried to afford 19.2 g (43%), of product, m.p. 158° dec. An additional 4.5 g of pure salt was obtained from the mother liquor making the total amount of product 23.7 g and the yield 53%. 3.0 g of product were recrystallized from ethanol to provide 2.80 g of N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboximide maleate. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1(CCC2=CC=CC=C12)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:CN1CCN(CC1)C1=NC2=C(N3C4=C1C=CC=C4CC3)C=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 21.1 g (0.0627 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 7a was added 500 ml of phosphorus oxychloride and this was refluxed under nitrogen overnight. The excess POCl3 was then removed at aspirator pressure with warming. The residue was boiled and triturated on the steam bath with 60 ml of absolute ethanol until solution resulted. This solution was cooled and stirred resulting in separation of a solid. This solid was collected, washed with ethanol, with ether, and finally hexane, then dried to afford 19.0 g. This was partitioned between 200 ml of chloroform and 100 ml of water, with good stirring. Addition of 2.5N-NaOH rendered the medium basic, and the product base passed into the organic phase. This was separated, washed twice with water, dried over Na2SO4 and concentrated to 6.5 g of an oil. This oil was boiled with 60 ml of acetone, filtered from some insolubles, and the filtrate concentrated under nitrogen to 20 ml and allowed to crystallize. This gave 2.6 g of solid, m.p. 144°-146° C. dec. This material was treated with 20 ml of 2N-HCl with stirring. The resulting solution was filtered from a small amount of insolubles, then made basic with 2.5N-NaOH and the product extracted into dichloromethane. The latter extract was washed twice with water, dried over Na2SO4, and concentrated to an oil which began to crystallize. This was quickly dissolved in a small volume of boiling acetone and allowed to crystallize. The crystals were collected, washed with a little acetone, and dried to afford 2.00 g (10% overall yield) of 6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 149°-151° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:ClC=1C=C2CCNC2=CC1;m1_m2_m3_m4:ClC1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CN(C=O)C, and Products are 0:ClC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Cl)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 123 g (0.80 mole) of 5-chloroindoline, 134 g (0.70 mole) of 1,4-dichloronitrobenzene and 97 g (0.80 mole) of collidine in 1000 ml of dimethylformamide was heated under nitrogen at 150° C. for 48 hours. The mixture was then cooled, filtered from some insolubles, and the solvent was removed in vacuo with warming. The residue was partitioned between 1000 ml of dichloromethane and 500 ml of water. The water layer was removed and the organic phase was washed twice with 2N-hydrochloric acid, once with 2N-sodium hydroxide, once more with water, dried over Na2SO4 and concentrated to an oil weighing 230 g. This was dissolved in 170 ml of methanol and stirred at room temperature and then at 0° C. The resultant crystals were collected, washed well with cold methanol, and dried. This afforded 86.5 g (40% yield) of product, m.p. 130°-133° C. 4 g of 5-chloro-1-(4-chloro-2-nitrophenyl)indoline were recrystallized from methanol in 85% yield (overall yield: 34%); m.p. 133°-135° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4_m3:ClC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Cl)[N+](=O)[O-];m1_m2_m4_m3:C1=CC=CC=C1, Reagents are:m1_m2_m4_m3:[Pt];m1_m2_m4_m3:C(C)O, and Products are 0:C(C)[O-].Cl.NC1=C(C=CC(=C1)Cl)N1CCC2=CC(=CC=C12)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A Parr bottle, charged with 12.4 g (0.040 mole) of 5-chloro-1-(4-chloro-2-nitrophenyl)indoline of Example 8a, 100 ml of benzene, 100 ml of absolute ethanol and 0.5 g of 1% Pt/C was shaken under an initial hydrogen pressure of 57 psig until uptake ceased. The catalyst was then removed by filtration and the filtrate was concentrated in vacuo to an oil weighing 11.2 g (100%). This was dissolved in 30 ml of ethanol and then 30 ml of ether saturated with hydrogen chloride was added. An additional 500 ml of plain ether was added, and the mixture was stirred at 0° C., to maximize precipitation. The hydrochloride salt was collected, dried, and found to weigh 9.2 g (73%), m.p. 174°-178° C. Recrystallization from ethanol (charcoal) afforded 1-(2-amino-4-chlorophenyl)-5-chloroindoline hydrochloride ethanolate in 58% overall yield, m.p. 177°-180° C. |
Here is a chemical reaction formula: Reactants are:m3_m4:FC1=C(C(=O)N)C=CC=C1;m1_m2:BrC=1C=C2CCNC2=CC1;m1_m2:[H-].[Na+], Reagents are:m3_m4:CS(=O)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C(=O)N)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A slurry was prepared from 5-bromoindoline (9.85 g, 50 mmoles) dimethylsulfoxide (DMSO) (35 ml), sodium hydride (2.6 g, 50% in oil, washed with hexane, 1.1 eq). The slurry was stirred for 30 minutes. To this a solution of o-fluorobenzamide (7.9 g, 1.1 eq) in DMSO (15 ml) was added dropwise with temperature between 12°-13° C. At the end of addition the reaction mixture was stirred at ambient temperature for 4 hours, then heated up to 55° C. for 24 hours. The reaction mixture was partitioned between dichloromethane (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with dichloromethane (DCM) (150 ml). The combined DCM solution was washed twice with water (100 ml), twice with 2N HCl (100 ml), twice with brine (50 ml), dried over Na2SO4 and concentrated to a solid. Purification was on a flash chromatographic column (150 gm of silica gel) eluted with dichloromethane (DCM) (3 l). This gave 6.4 g of product (40%). Recrystallization from a small amount of ether yielded the 2-(5-bromo-indolin-1-yl)benzamide, m.p. 120°-122° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC=C4)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of N-[2-(5-bromo-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide (11.5 g, 27.5 mmoles) and 750 ml of phosphorus oxychloride was stirred until a solution was obtained and then heated under reflux for 40 minutes. The reaction mixture was cooled. Excess phosphorus oxychloride was removed by evaporation at 50°-55° C. The residue was dried for 30 minutes under vacuum. Ice-chilled 2N sodium hydroxide solution (250 ml) and dichloromethane (350 ml) were added to the residue at 4° C. (ice-water bath). The mixture was stirred until all the solid had dissolved. The organic phase was separated and washed with brine (2 times, 200 ml), dried over anhydrous magnesium sulfate and concentrated. Crystallization from ether (100 ml) gave 5.7 g (57%) of product. Recrystallization from isopropanol yielded the analytical sample, mp 203°-204° C. |
Here is a chemical reaction formula: Reactants are:m2:C1(=CC=CC=C1)N1CCNCC1;m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1;m3:[OH-].[Na+], Reagents are:m4:[Ti](Cl)(Cl)(Cl)Cl;m1_m5:C1(=CC=CC=C1)C, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C2=CC=CC=C2)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 7.88 g (0.0250 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-one and 1200 ml of toluene was heated under nitrogen until a solution resulted. Then there was added 40.6 g (0.250 mole) of N-phenylpiperazine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for three hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated to an oil. The oil was taken up in 80 ml of hot methanol, from which the product crystallized, affording 7.8 g (68%) of product. Recrystallization from a hot solution of dichloromethane (25 ml), to which methanol (25 ml) was added, provided the analytical sample, mp 171°-173° C. |
Here is a chemical reaction formula: Reactants are:m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1;m3:[OH-].[Na+];m2:C(CC)N1CCNCC1, Reagents are:m1_m5:C1(=CC=CC=C1)C;m4:[Ti](Cl)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)CCC)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 7.88 g (0.0250 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated until a solution resulted. Then there was added 32.1 g (0.25 mole) of N-propylpiperazine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was refluxed for 3 hours, and then cooled to room temperature. The mixture was stirred with 500 ml of 2N sodium hydroxide solution for 15 minutes and the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, filtered, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated to an oily solid. The oily solid was dissolved in 25 ml of hot ethyl acetate, filtered, and allowed to crystallize first at room temperature, then at 0° C. to yield 3.20 g (30%) of product, mp 134°-136° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC=C4)N4CCN(CC4)C)C1, Reagents are:m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[O-2].[Mn+4], and Products are 0:ClC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC=C4)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-chloro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (6 g, 17 mmoles), in chloroform (150 ml) was added manganese dioxide (10.5 g). The mixture was heated under reflux for 24 hours. The mixture was cooled, filtered and the solid was washed with dichloromethane (200 ml). The filtrate was then concentrated to dryness. The residue was purified by flash chromatography over a silica gel column (150 g), eluted with 2% methanol in dichloromethane (4 l) and 3% methanol in dichloromethane (2 l). Evaporation of the eluent gave 3.8 g (63%) of product. Recrystallization from toluene (40 ml) yielded the analytical sample, mp 170°-172° C. |
Here is a chemical reaction formula: Reactants are:m2:CC1CCNCC1;m1_m4:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1, Reagents are:m1_m4:C1(=CC=CC=C1)C;m3:[Ti](Cl)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCC(CC2)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4.73 g (0.0150 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1000 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 14.9 g (0.150 mole) of 4-methylpiperidine, followed by 8.54 g (0.045 mole) of titanium tetrachloride. The mixture was refluxed for 3 hours, cooled to room temperature and filtered. The filtrate was stirred with 500 ml of 2N sodium hydroxide solution for 15 minutes and the layers were separated. The aqueous phase was extracted with 250 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to an oil which solidified. The solid was triturated twice with hexane to afford 4.9 g (83%) of product. Recrystallization from ethyl acetate provided the analytical sample, mp 177°-179° C. |
Here is a chemical reaction formula: Reactants are:m1_m5:BrC1=CC2=C(N3C4=C(C(N2)=O)C=CC=C4CC3)C=C1;m3:[OH-].[Na+];m2:N1CCSCC1, Reagents are:m1_m5:C1(=CC=CC=C1)C;m4:[Ti](Cl)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N2CCSCC2)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 7.88 g (0.025 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 25.8 g (0.250 mole) of thiomorpholine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for 3 hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was crystallized from 100 ml of hot methanol to give 8.8 g (88%) of product. Recrystallization from a hot solution of dichloromethane (50 ml, charcoal) to which methanol (100 ml) was added provided the analytical sample, mp 165°-167° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=CC(=C(C1)NC(=O)N(C)C)N1CCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC1=CC2=C(N3C4=C(C(=N2)N(C)C)C=CC=C4CC3)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 10.8 g (0.030 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-N',N'-dimethylurea and 110 ml of phosphorus oxychloride, under nitrogen, was heated under reflux for 6 hours, with stirring, and then cooled to room temperature. The excess phosphorus oxychloride was removed under vacuum with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and treated first with 250 ml of ice-cold 2N sodium hydroxide solution, and then with 500 ml of dichloromethane. The mixture was stirred and triturated until all the material passed into solution. The organic phase was separated, washed with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to an oil. The oil was dissolved in 50 ml of ethyl acetate and the solution was concentrated under a stream of nitrogen. At a volume of about 30 ml, the mixture was filtered. Concentration of the filtrate was continued to a volume of about 20 ml, during which crystallization resulted. The solid was dissolved by heating, the hot solution was filtered and allowed to crystallize to afford 4.9 g (48%) of product, mp 124°-127° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4_m3:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C(=O)O)C=CC=C1, Reagents are:m1_m2_m4_m3:Cl;m1_m2_m4_m3:[Pd];m1_m2_m4_m3:C(C)O, and Products are 0:CC=1C=C2C=3N(C4=C(C(N2)=O)C=CC=C4)CCC3C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 2-(5-methyl-7-nitroindolin-1-yl)benzoic acid (9 g, 0.03 mole), conc. hydrochloric acid (several drops) and ethanol (200 ml) was added 5% palladium-charcoal (1.5 gm). The mixture was shaked under hydrogen (58 psi) for 30 hours. The solvent was removed and the residue was loaded onto a silica gel flash chromatography column (800 g, 230-400 mesh), packed and eluted with dichloromethane (4 l) and 2% methanol in dichloromethane (4 l). The fractions containing product were pooled and evaporated to yield 5 g (66%) of product. Recrystallization from chloroform gave the analytical sample, mp 222°-224° C. |
Here is a chemical reaction formula: Reactants are:m8:O;m6_m7:C([O-])(O)=O.[Na+];m6_m7:CN(C(=O)Cl)C;m4_m5:C([O-])(O)=O.[Na+];m4_m5:CN(C(=O)Cl)C;m1_m2_m9_m3_m10:Cl.NC1=C(C=CC(=C1)Br)N1CCC2=CC=CC=C12;m1_m2_m9_m3_m10:C([O-])(O)=O.[Na+];m1_m2_m9_m3_m10:CN(C(=O)Cl)C, Reagents are:m1_m2_m9_m3_m10:C(Cl)(Cl)Cl;m1_m2_m9_m3_m10:C(Cl)(Cl)Cl, and Products are 0:BrC=1C=CC(=C(C1)NC(=O)N(C)C)N1CCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred mixture, under nitrogen, of 28.9 g (0.10 mole) of 1-(2-amino-4-bromophenyl)indoline hydrochloride and 16.8 g (0.20 mole) of anhydrous powdered sodium bicarbonate in 500 ml of chloroform was added a solution of 21.5 g (0.20 mole) of dimethylcarbamyl chloride in 25 ml of chloroform, over a 10 minute period. The mixture was heated under reflux for 7 hours, and 8.4 g (0.10 mole) of sodium bicarbonate and 10.7 g (0.10 mole) of the dimethylcarbamyl chloride were added. After heating under reflux for 2 days, equivalent amounts (8.4 g of sodium bicarbonate and 10.7 g of dimethylcarbamyl chloride) were added. After three days under reflux, the mixture was cooled and 500 ml of water was added. The phases were stirred vigorously for 0.5 hours and separated. The organic phase was washed three times with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in 200 ml of dichloromethane and adsorbed on a chromatography column containing 1 kg of silica gel packed in and eluted with dichloromethane. The fractions containing product were combined and concentrated to afford 14.5 g (40%) of product. Recrystallization from toluene (charcoal)/hexane gave the analytical sample, mp 119°-121° C. |
Here is a chemical reaction formula: Reactants are:m4:ClCCl;m1_m2_m3_m5:BrC=1C=C2CCNC2=CC1;m1_m2_m3_m5:N1=C(C=C(C=C1C)C)C;m1_m2_m3_m5:FC1=C(C=CC=C1)[N+](=O)[O-], Reagents are:m1_m2_m3_m5:C=1(C(=CC=CC1)C)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-Bromoindoline (4.0 g, 0.02 mole), collidine (3.6 g, 0.03 mole), and o-fluoronitrobenzene (2.8 g, 0.02 mole) in xylene (25 ml) were heated at 185° C. (oil bath temperature) for 24 hours. The mixture was cooled to room temperature and poured into dichloromethane. The dichloromethane solution was washed with 1N hydrochloric acid (3 times, 150 ml), brine (200 ml), dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated. Crystallization of the residue was induced by stirring in ether (15 ml) followed by hexane (200 ml), then chilling in the refrigerator overnight. The solid was filtered and washed with hexane and dried to yield 3.5 g (55%) of product. Recrystallization from 2-propanol yielded the analytical sample, mp 12°-114° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m5:[OH-].[K+];m1_m4_m5:C(CO)O;m3_m6:ClCCl;m2:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C#N)C=CC=C1, Reagents are:m1_m4_m5:O;m3_m6:O, and Products are 0:CC=1C=C2CCN(C2=C(C1)[N+](=O)[O-])C1=C(C(=O)O)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution under nitrogen of potassium hydroxide (30 g, 0.53 mole) in ethylene glycol (250 ml) and water (35 ml) was heated to 175° C., at which temperature there was added 2-(5-methyl-7-nitroindolin-1-yl)benzonitrile (26 g, 0.093 mole). After heating at 175° C. for 3 hours, the reaction mixture was cooled to room temperature and dichloromethane (1 liter) and water (500 ml), were added, with stirring. The aqueous phase was separated and extracted with two 250 ml-portions of dichloromethane. The aqueous phase was then cooled in an ice-bath and acidified with concentrated hydrochloric acid. The product was extracted out with three 500 ml-portions of dichloromethane. The combined organic extracts were washed twice with brine, dried, filtered, and concentrated to afford 9.0 g (32%) of product. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)N(C([O-])=O)C1=CC=CC=C1;m1_m2_m3:CN1CCNCC1, Reagents are:m1_m2_m3:CCOCC, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=CC=C1)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)phenyl]phenylcarbamate (11.5 g, 28.5 mmoles), N-methylpiperazine (15 ml) and ether (50 ml) was stirred at room temperature for 2 hours. The ether was evaporated. The mixture was filtered through a silica gel column (150 g), packed with dichloromethaane, and the column was washed with 2% methanol-dichloromethane solution (2 l). The solvent was evaporated. The residue was purified by flash chromatography on a silica gel column (150 g, 230-400 mesh), eluted with 1% methanol/dichloromethane (4 l), 1.5% methanol/dichloromethane (2 l), and 2% methanol/dichloromethane. The fractions containing the desired material were collected and evaporated to give 10.9 g (90%) of product. Crystallization from chloroform and hexane afforded the analytical sample, mp 108°-110° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:FC1=C(C=CC=C1)[N+](=O)[O-];m1_m2_m3_m4:N1CCCC2=CC=CC=C12;m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CC1=C(C(=CC=C1)C)C, and Products are 0:[N+](=O)([O-])C1=C(C=CC=C1)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture, under nitrogen of 70.6 g (0.50 mole) of 1-fluoro-2-nitrobenzene, 133.2 g (1.00 mole) of 1,2,3,4-tetrahydroquinoline and 121.2 g (1.00 mole) of symmetrical collidine in 500 ml of 1,2,3-trimethylbenzene was refluxed (bp 178°) for 5 days. The mixture was concentrated in vacuo. The residue was taken up in 1000 ml of chloroform and extracted with 500 ml of 2N-hydrochloric acid. The aqueous phase was back extracted with 250 ml of chloroform. The combined organic layers were washed 3 times with 2N-hydrochloric acid, once with 2N-sodium hydroxide solution, twice with water and dried over anhydrous sodium sulfate. The solvent was removed in vacuo. The residual oil was dissolved in 300 ml of 1:1 hexane:toluene and adsorbed on a chromatography column containing 2 kg of silica gel packed in hexane. Elution with 1:1 hexane:toluene gave fractions containing product. The fractions were combined and concentrated to afford 28.2 g (22%) of product. Recrystallization from hot isopropyl ether afforded the analytical sample, mp 69°-71° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)C)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)C)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide (3.3 g, 7.68 mmoles) and phosphorus oxychloride (30 ml) was heated at reflux for 25 minutes under nitrogen. The solution was cooled and excess phosphorus oxychloride was removed at 55°-60° C. under vacuum. Ice-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml) were added to the residue. The organic phase was separated and washed with brine (2 times, 100 ml), dried over anhydrous magnesium sulfate, and concentrated. Purification was accomplished by flash chromatography over aluminum oxide (Grade III, 100 g), eluted with dichloromethane (2 l). The fractions containing pure material were pooled and concentrated. Recrystallization from isopropanol (30 ml) yielded 1.7 g (53.9%) of product, mp 187°-189° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:BrN1C(CCC1=O)=O;m1_m4_m2_m5:CN1CCN(CC1)C1=NC2=C(N3C4=C1C=CC=C4CC3)C=CC(=C2)C;m3:ClCCl, Reagents are:m1_m4_m2_m5:CN(C=O)C;m1_m4_m2_m5:CN(C=O)C, and Products are 0:BrC=1C(=CC2=C(N3C4=C(C(=N2)N2CCN(CC2)C)C=CC=C4CC3)C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-bromosuccinimide (0.91 g, 5.1 mmoles) in dimethylformamide (3 ml) was added dropwise to a solution of 6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (1.6 g, 4.8 mmoles) in dimethylformamide (30 ml) at 0°-3° C. The reaction mixture was stirred for 30 minutes. The solution was poured into dichloromethane (250 ml), and was washed with brine (4 times, 150 ml), and dried over anhydrous magnesium sulfate. The solvent was removed at reduced pressure and the residue was dried. Purification was accomplished by flash chromatography on an aluminium oxide column (grade III, 60 g), eluted with dichloromethane (500 ml) and 2% methanol in dichloromethane (250 ml). The fractions containing the product were pooled and concentrated. Recrystallization from 2-propanol:water (1:1, 20 ml) yielded 230 mg (11.6%) of product, mp 177°-177° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)C)N4CCN(CC4)C)C1, Reagents are:m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[O-2].[Mn+4], and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC(=C4)C)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-bromo-6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (5.7 g, 13.8 mmoles) in chloroform (540 ml) was added manganese dioxide (25 gm), and the mixture was heated under reflux for 4 days. The mixture was filtered, and the filter cake washed with dichloromethane. The filtrate was concentrated under vacuum. The residue was purified on a silica gel column, eluted with 2% methanol/dichloromethane. The fractions (75-100 ml each) containing pure product were pooled and concentrated. Recrystallization from a small volume of 2-propanol yielded 2.41 g (42%) of product, mp 153°-155° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)C)[N+](=O)[O-];m1_m2_m3_m4:ClCCl, Reagents are:m1_m2_m3_m4:C(C)O;m1_m2_m3_m4:[Pt], and Products are 0:Cl.NC1=C(C=CC(=C1)C)N1CCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a warm solution of 4-(5-bromo-1-indolinyl)-3-nitrotoluene (10 g, 0.03 mole) in dichloromethane (40 ml) and ethanol (160 ml) was added 1% platinum-on-carbon (2.0 gm). The mixture was shaken under hydrogen (57 psi) for 3.5 hours. The mixture was filtered and concentrated. The residue was dried under vacuum at 55° C. Purification was accomplished by flash chromatography over silica gel (100 g), eluted with a mixture of hexane:dichloromethane (3:1, 2 l and 1:1, 1 l). The fractions containing pure product were pooled and concentrated. The residue was dissolved in ether (250 ml) and added to a methanol/hydrogen chloride solution, and the mixture was stirred at 0° C. for 10 minutes. The precipitate was filtered and dried to afford 4.0 g (39%) of product, mp 195°-200° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:[N+](=O)([O-])C1=C(C=CC(=C1)Br)N1CCC2=CC=CC=C12;m1_m4_m2_m5:BrN1C(CCC1=O)=O;m3:O, Reagents are:m1_m4_m2_m5:CN(C=O)C;m1_m4_m2_m5:CN(C=O)C, and Products are 0:[N+](=O)([O-])C1=C(C=CC(=C1)Br)N1CCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 1-(2-nitro-4-bromophenyl)indoline (15 g, 0.047 moles) in dimethylformamide (150 ml) at -10° C. was added dropwise a solution of N-bromosuccinimide (9.4 g, 0.054 mole) in dimethylformamide (50 ml) over 10 minutes. The reaction mixture was stirred at 0° C. for 15 minutes. The solution was added slowly to water (1 l) with vigorous stirring. The solid was filtered, dried, and dissolved in dichloromethane (300 ml). The solution was added to boiling methanol (1 l). The precipitate was collected by filtration to give 12.7 g (68%) of product, mp 150°-152° C. |
Here is a chemical reaction formula: Reactants are:m3:ClCCl;m1_m2_m4:BrN1C(CCC1=O)=O;m1_m2_m4:N1(CCC2=CC=CC=C12)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2_m4:CN(C=O)C, and Products are 0:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-Bromosuccinimide (2.6 g, 14.5 mmoles) was added to a solution of N-[2-(indolin-1-yl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide (5.0 g, 12.0 mmoles) in dimethylformamide (50 ml). The solution was stirred at room temperature for 15 minutes and at 60° C. for 15 minutes. The solution was cooled and poured into dichloromethane (500 ml). The layers were separated and the organic phase was washed with water (3×500 ml), brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was concentrated. The residue was purified by chromatography over silica gel (60 g, eluted with 4% methanol:96% dichloromethane, 1 l). The appropriate fractions were pooled and concentrated to give 4.8 g (84%) of product. Recrystallization from chloroform and hexane gave the analytical sample, mp 118°-119.5° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=C2CCN(C2=CC1)C1=C(C=C(C=C1)Br)NC(=O)N1CCN(CC1)C, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)Br)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of N-[2-(5-bromo-1-indolinyl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide (12.3 g, 24.8 mmoles) and phosphorus oxychloride (250 ml) was heated under reflux for 1 hour. The reaction mixture was cooled and then concentrated at 50°-60° C. under vacuum. Ice-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml) was added to the reaction mixture. The mixture was stirred for 20 minutes. The organic phase was separated and the aqueous phase was extracted once with dichloromethane (250 ml). The combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml), dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The residue was purified on a silica gel column (250 gm), eluted with 2% and then 3% methanol:dichloromethane. The appropriate fractions were combined and concentrated to give 8.3 g (70%) of product. Recrystallization from isopropanol gave the analytical sample, mp 215°-216° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:BrC=1C=C2C3=C(C(=NC4=C(N3CC2)C=CC(=C4)Br)N4CCN(CC4)C)C1, Reagents are:m1_m3_m2:C(Cl)(Cl)Cl;m1_m3_m2:[O-2].[O-2].[Mn+4];m4:[O-2].[O-2].[Mn+4], and Products are 0:BrC=1C=C2C3=C(C(=NC4=C(N3C=C2)C=CC(=C4)Br)N4CCN(CC4)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture 4,9-dibromo-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]-benzodiazepine (4.5 g, 9.45 mmoles) and manganese(IV) dioxide (7.0 g) in chloroform (150 ml) was heated under reflux for 3.5 hours. An additional 4.5 g of manganese dioxide was added. The reaction mixture was stirred overnight at room temperature. The mixture was filtered through celite and the filtrate was concentrated. The residue was purified by flash chromatography over a silica gel column (140 gm), eluted with 2% methanol:98% dichloromethane (2 l). The appropriate fractions were collected and evaporated. Crystallization of the residue from isopropanol (10 ml) yielded 3.37 g (75%) of product, mp 158°-159° C. |
Here is a chemical reaction formula: Reactants are:m1_m4:[N+](=O)([O-])C1=C(C=CC=C1)N1CCCC2=CC=CC=C12;m2_m5:BrN1C(CCC1=O)=O;m3:[OH-].[Na+], Reagents are:m1_m4:CN(C=O)C;m2_m5:CN(C=O)C, and Products are 0:BrC=1C=C2CCCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen, of 1-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (76.3 g, 0.30 mole) in dimethylformamide (1000 ml) was cooled to -10° C. A solution of of N-bromosuccinimide (58.7 g, 0.33 mole) in dimethylformamide (250 ml) was added dropwise at such a rate as to keep the reaction temperature below 0° C. (1.5 hours). Half-an hour after the addition was completed, the reaction mixture was poured into 7 liters of 2N-sodium hydroxide solution/ice, with stirring. The product separated as an oil. The quench fluids were decanted and the oil was rinsed several times with water. The oil was dissolved in dichloromethane (1.5 l). The organic solution was extracted once with 2N-sodium hydroxide solution, thrice with water, dried over sodium sulfate and concentrated. The residue was dissolved in 1:1 hexane:toluene (250 ml) and the solution was absorbed on a chromatography column containing 2 kg of silica gel packed in 1:1 hexane:toluene. Elution with this solvent mixture provided 82.7 g (82%) of product, as an oil. For analysis, a sample was Kugelrohr distilled at a vessel temperature of 166°-168° C. (0.2 mm Hg). |
Here is a chemical reaction formula: Reactants are:m4_m5:C(\C=C/C(=O)O)(=O)O;m1_m6_m2_m3:BrC=1C=C2CCCN(C2=CC1)C1=C(C=CC=C1)[N+](=O)[O-];m1_m6_m2_m3:C1=CC=CC=C1;m1_m6_m2_m3:C(C)O, Reagents are:m4_m5:CCOCC;m1_m6_m2_m3:[Pt], and Products are 0:C(\C=C/C(=O)O)(=O)O.NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A Parr hydrogenation bottle was charged with 6-bromo-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (16.7 g, 0.050 mole), 1% platinum-on-carbon (1 g), benzene (100 ml) and ethanol (100 ml). The mixture was shaken under an initial hydrogen pressure of 58 psi until uptake ceased. The mixture was then filtered to remove the catalyst and the filtrate was concentrated under vacuum. The residue was taken up in hot ether (150 ml), filtered, and the filtrate was treated with a hot solution of maleic acid (6.4 g, 0.055 mole) in ether (500 ml). The solution was boiled down to about 300 ml and allowed to cool. The supernatant was decanted from an oil, which separated. The supernatant was concentrated and the process was repeated several times to give 11.4 g (55%) of product. Recrystallization from ethyl acetate afforded the analytical sample, mp 113°-116° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m7:NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br;m1_m2_m7:C(C)N(CC)CC;m6_m10:C(\C=C/C(=O)O)(=O)O;m4_m8:CN1CCNCC1;m5:CN1CCNCC1;m3:C1(=CC=CC=C1)OC(=O)Cl, Reagents are:m1_m2_m7:ClCCl;m6_m10:C(C)O;m11:O;m9:ClCCl;m4_m8:ClCCl, and Products are 0:C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen, of 1-(2-aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline (21.2 g, 0.070 mole) and triethylamine (10.1 g, 0.10 mole) in dichloromethane (200 ml) was cooled to 0° C. Then there was added dropwise phenylchloroformate (15.7 g, 0.10 mole) at such a rate as to keep the reaction temperature below 5° C. The addition took 30 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 2 hours at room temperature, and N-methylpiperazine (28.1 g, 0.28 mole) dissolved in dichloromethane (30 ml) was added dropwise over a 45 minute period. The solution was stirred for 3 hours and an additional charge of N-methylpiperazine (14.05 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added, and the mixture was stirred overnight. Water (250 ml) was added with vigorous stirring. The layers were separated and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in ethanol (200 ml), with heating, and treated with a warm solution of maleic acid (8.93 g, 0.077 mole) in ethanol (100 ml). The maleate salt was collected to give 23.2 g (61%) of product. Recrystallization from methanol afforded the analytical sample, mp 172°-174° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC(=CC=C12)Br, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=C2CCCN3C2=C(C(=NC2=C3C=CC=C2)N2CCN(CC2)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 4-methyl-N-[2-(6-bromo-1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazine-carboxamide (14.2 g, 0.0330 mole) in phosphorus oxychloride (250 ml) was heated under reflux under nitrogen for 5 hours. The reaction mixture was cooled to room temperature and excess phosphorous oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (500 ml). The mixture was stirred, the organic phase was separated, washed with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was digested in boiling methanol (40 ml) to afford 10.7 g (79%) of product. Recrystallization from ethanol provided the analytical sample, mp 181°-183° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:BrC1=C(C=C(C=C1)Br)[N+](=O)[O-];m1_m2_m3_m4:N1CCCC2=CC=CC=C12;m1_m2_m3_m4:N1=C(C=C(C=C1C)C)C, Reagents are:m1_m2_m3_m4:CC1=C(C(=CC=C1)C)C, and Products are 0:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture, under nitrogen, of 2,5-dibromonitrobenzene (140.5 g, 0.50 mole), 1,2,3,4-tetrahydroquinoline (133.2 g, 1.00 mole) and symmetrical collidine (121.2 g, 1.00 mole) in 1,2,3-trimethylbenzene (500 ml) as solvent was heated at 160°-165° C. for 7 days. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated in vacuo (100° C.). The residue was taken up in dichloromethane (1.5 l) and the solution was extracted three times with dilute hydrochloric acid, once with dilute sodium hydroxide solution, three times with water, dried over anhydrous sodium sulfate and concentrated. This residue was dissolved in 1:1 hexane:toluene (250 ml) and adsorbed on a chromatography column containing 3 kg of silica gel. Elution with 1:1 hexane:toluene gave 30 g (18%) of product, as an oil. A portion of the oil was Kugelrohr distilled at an oven-temperature of 163°-165° C. (0.1 mm Hg) to provide the analytical sample. |
Here is a chemical reaction formula: Reactants are:m2:C(C)O;m1_m3:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)[N+](=O)[O-], Reagents are:m4:[Pt];m1_m3:C1=CC=CC=C1, and Products are 0:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-(4-Bromo-2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (11.6 g, 0.035 mole) was dissolved in benzene (125 ml), and ethanol added (75 ml), followed by 1% platinum-on-charcoal (0.40 g). The mixture was shaken under an initial pressure of 56 psi for 6.5 hours. The mixture was filtered and the filtrate was evaporated at 50° C. under vacuum to provide 10.6 g (100%) of product, as a gum. |
Here is a chemical reaction formula: Reactants are:m5_m9:CN1CCNCC1;m3:C1(=CC=CC=C1)OC(=O)Cl;m4:C1(=CC=CC=C1)OC(=O)Cl;m1_m6:BrC1=CC(=C(C=C1)N1CCCC2=CC=CC=C12)N;m2:C(C)N(CC)CC, Reagents are:m5_m9:ClCCl;m10:O;m1_m6:ClCCl;m8:ClCCl, and Products are 0:CN1CCN(CC1)C(=O)NC1=C(C=CC(=C1)Br)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-(4-Bromo-2-aminophenyl)-1,2,3,4-tetrahydroquinoline (10.6 g, 0.035 mole) was dissolved on a steam bath in dichloromethane (150 ml). The solution was cooled to -5° C. in ice/methanol and triethylamine (5.01 g, 0.050 mole) was added in one portion, followed by a solution of phenylchloroformate (7.85 g, 0.050 mole) dissolved in dichloromethane (10 ml), dropwise over 15 minutes. The mixture was stirred 1 hour in the cold, 2 hours at room temperature, and an additional charge of phenylchloroformate (1.57 g, 0.010 mole) was added. After one hour, a solution of N-methylpiperazine (14.1 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added over 0.5 hour. The reaction mixture was stirred under nitrogen at room temperature overnight. Water (100 ml) was added and the mixture was stirred 0.5 hour. The organic phase was separated, washed 4 times with water, dried over anhydrous sodium sulfate, and evaporated in a 100° C. bath in vacuo. The residue was dissolved in toluene (40 ml), adsorbed on a column of silica gel (500 g) packed in toluene and eluted with dichloromethane-methanol (98:2). The appropriate fractions were combined and evaporated to give 9.2 g (61%) of product, as an oil. |
Here is a chemical reaction formula: Reactants are:m1_m2:CN1CCN(CC1)C(=O)NC1=C(C=CC(=C1)Br)N1CCCC2=CC=CC=C12, Reagents are:m1_m2:P(=O)(Cl)(Cl)Cl, and Products are 0:BrC=1C=CC2=C(N=C(C3=C4N2CCCC4=CC=C3)N3CCN(CC3)C)C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of 4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide (8.6 g, 0.020 mole) in phosphorus oxychloride (200 ml) was heated under reflux under nitrogen for 6 hours. The reaction mixture was cooled to room temperature and excess phosphorus oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml). The mixture was stirred and triturated until the residue dissolved. The organic phase was separated, washed again with 2N sodium hydroxide solution, twice with water, dried over sodium sulfate, and concentrated in vacuo. The residue was taken up in 4N hydrochloric acid (100 ml), filtered, and the filrate was stirred 15 minutes with charcoal. After filtration, the solution was stirred with dichloromethane (100 ml), and the mixture was made alkaline by the addition of cold 2N sodium hydroxide solution. The organic phase was separated, washed twice with water, dried over sodium sulfate, and boiled 15 minutes with charcoal. After filtration, the solution was concentrated to give 4.6 g (56%) of product, as an oil, which crystallized on standing. The product was taken up in boiling methanol (20 ml) and allowed to crystallize first at room temperature, then in the refrigerator. Recrystallization from methanol afforded the analytical sample, mp 153°-156° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m7:NC1=C(C=CC=C1)N1CCCC2=CC=CC=C12;m1_m2_m7:C(C)N(CC)CC;m4:CN1CCNCC1;m3:C1(=CC=CC=C1)OC(=O)Cl;m5:CN1CCNCC1;m6_m8:C(\C=C/C(=O)O)(=O)O, Reagents are:m1_m2_m7:ClCCl;m6_m8:C(C)O;m9:O, and Products are 0:C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C(=O)NC1=C(C=CC=C1)N1CCCC2=CC=CC=C12, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution, under nitrogen of 1-(2-aminophenyl)-1,2,3,4-tetrahydroquinoline (4.50 g, 0.020 mole), and triethylamine (3.04 g, 0.030 mole) in dichloromethane (50 ml) was cooled to 0° C. and phenylchloroformate (4.70 g, 0.030 mole) was added dropwise at such a rate such as to keep the reaction temperature below 5° C. The addition took 10 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 1 hour at room temperature, and N-methylpiperazine (8.02 g, 0.080 mole) was added dropwise over a 5 minute period. The solution was stirred for 2 hours, N-methyl-piperazine (4.01 g, 0.040 mole) was added and the solution was stirred overnight. Water (100 ml) was added with vigorous stirring. The layers were separated, and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in ethanol (100 ml) and treated with a warm solution of maleic acid (2.6 g 0.022 mole) in ethanol (15 ml). The precipitate was collected to provide 6.1 g (65%) of product. Recrystallization from methanol afforded the analytical sample, mp 171°-173° C. dec. |
Here is a chemical reaction formula: Reactants are:m3:CC(=O)C.OS(=O)(=O)O.O=[Cr](=O)=O;m2_m4:CC(=O)C;m1:OCC=1OC=C(C(C1)=O)OCC1=CC=CC=C1, Reagents are:m2_m4:O, and Products are 0:O=C1C=C(OC=C1OCC1=CC=CC=C1)C(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 232 g (1 mol) of 2-(hydroxymethyl)-5-(phenylmethoxy)-4H-pyran-4-one was put into a 10 l stirring flask containing 6.6 l of acetone and 400 ml of water. The clear solution was cooled to +5° C. by means of an ice bath. While maintaining the temperature at +5° C. to 10° C., 640 ml of Jones reagent (202 g CrO3, 600 ml water, 174 ml H2SO4) was added dropwise over a period of 1 hour. Stirring was continued for 2 hours without cooling. The reaction mixture was filtered through a glass frit and the dark green residue washed with 500 ml of acetone. The filtrate was then evaporated until all of the acetone was removed. To the aqueous, partly crystalline product was added 1.2 l of methanol, and this mixture was then heated to its boiling point. The resulting clear dark green solution was placed in an ice bath and the product allowed to crystallize. The crystalline product was filtered and washed with 500 ml of a cold solvent mixture consisting of 250 ml of methanol +250 ml of water and finally dried. Yield: 195 g. From the mother liquor, a further 5% of the product could be isolated. |
Here is a chemical reaction formula: Reactants are:m1_m4_m5_m2:C1(=CC=CC=C1)COC1=CC(=NC=C1OCC1=CC=CC=C1)C(=O)OCC1=CC=CC=C1;m1_m4_m5_m2:[OH-].[K+];m3:Cl, Reagents are:m1_m4_m5_m2:O1CCCC1;m1_m4_m5_m2:O;m6:O, and Products are 0:C1(=CC=CC=C1)COC1=CC(=NC=C1OCC1=CC=CC=C1)C(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4,5-bis(phenylmethoxy)-2-pyridinecarboxylic acid, phenylmethyl ester (1.60 g, 3.76 mmole) in 15 ml of tetrahydrofuran and 2.2 ml of water was added 4 ml of 1N aqueous potassium hydroxide. The mixture was stirred at room temperature overnight. Water (15 ml) was added and 1N hydrochloric acid was added slowly with stirring while monitoring the pH. The pH of the mixture fell steadily to ca. 6.2 whereupon a large amount of solid began to separate and no further decrease in the pH was noted. Continued addition of hydrochloric acid eventually effected a sudden drop in pH to 3.2 and the addition was stopped. The solid was filtered and washed well with water, then ether, and dried in vacuo to afford 1.197 g of the title compound as a white waxy solid. |
Here is a chemical reaction formula: Reactants are:m1:FC(C(=O)O)(F)F;m2_m3_m5_m4:OC=1C(C=C(NC1)C(COP(=O)(N1[C@H]([C@@H](C1=O)NC(OC(C)(C)C)=O)C)O)=O)=O;m2_m3_m5_m4:[K];m2_m3_m5_m4:C1(=CC=CC=C1)OC, Reagents are:m6:C1(=CC=CC=C1)C;m2_m3_m5_m4:ClCCl, and Products are 0:FC(C(=O)O)(F)F.N[C@H]1[C@@H](N(C1=O)P(O)(=O)OCC(=O)C=1NC=C(C(C1)=O)O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Trifluoroacetic acid (3 ml) was added to a 5° C. stirred suspension of (2S-trans)-[1-[[2-(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)-2-oxoethoxy]hydroxyphosphinyl]-2-methyl-4-oxo-3-azetidinyl]carbamic acid, 1,1-dimethylethyl ester, monopotassium salt (375 mg) in 4 ml of dry dichloromethane containing 1 ml of anisole. After about three minutes, the solid dissolved and the mixture was stirred for 1.25 hours at 5° C. TLC indicated the reaction was essentially complete. Toluene (2 ml) was added and the mixture was concentrated in vacuo to a viscous brown oil. The oil was washed twice with hexane, then triturated with ether. The resultant solid was washed twice with ether and dried in vacuo to afford 0.437 g of crude title compound, which was used directly in the next step. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:OCC=1OC=C(C(C1)=O)OCC1=CC=CC=C1;m1_m2_m3:C(C1=CC=CC=C1)N, Reagents are:m1_m2_m3:O, and Products are 0:OCC=1N(C=C(C(C1)=O)OCC1=CC=CC=C1)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 2-(hydroxymethyl)-5-(phenylmethoxy)-4H-pyran-4-one (10.5 g, 45.3 mmol) in benzylamine (40 ml) and water (60 ml) was refluxed for four hours and then stirred overnight at room temperature. The resulting precipitate was collected and washed thoroughly with water to give 9.17 g (28.6 mmol) of 2-(hydroxymethyl)-5-(phenylmethoxy)-1-(phenylmethyl)-4(1H)pyridinone (melting point 146°-147° C.) upon drying. The supernatant was diluted with water to a total volume of 450 ml, and after standing for one hour at room temperature, the resulting precipitate was collected to yield 2.47 g (7.69 mmol) of additional 2-(hydroxymethyl)-5-(phenylmethoxy)-1-(phenylmethyl)-4(1H)-pyridinone upon drying. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClCC(=O)NC1=CC(=C(C=C1)OCC1=CC=CC=C1)OCC1=CC=CC=C1;m1_m2_m3:[I-].[Na+], Reagents are:m1_m2_m3:CC(=O)C, and Products are 0:ICC(=O)NC1=CC(=C(C=C1)OCC1=CC=CC=C1)OCC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 2-chloro-N-[3,4-bis(phenylmethoxy)phenyl]acetamide (8.98 g, 23.5 mmol) and sodium iodide (3.53 g, 23.5 mmol) in acetone (75 ml) was refluxed for two hours and allowed to stand overnight at room temperature. The reaction was filtered hot to remove the sodium iodide and a precipitate formed in the cold filtrate which was collected and washed with cold acetone to give, upon drying, 6.71 g (14.2 mmol) of the title compound. A second crop was obtained from cold acetone (1.0 g). |
Here is a chemical reaction formula: Reactants are:m1_m2_m5:OC=1C=C(C=CC1O)C(COP(=O)(N1[C@H]([C@@H](C1=O)NC(OC(C)(C)C)=O)C)O)=O;m1_m2_m5:[K];m3:C1(=CC=CC=C1)OC;m4:FC(C(=O)O)(F)F, Reagents are:m1_m2_m5:ClCCl;m6:C1(=CC=CC=C1)C, and Products are 0:FC(C(=O)O)(F)F.N[C@H]1[C@@H](N(C1=O)P(OCC(=O)C1=CC(=C(C=C1)O)O)(O)=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of (2S-trans)-[1-[[2-(3,4-dihydroxyphenyl)-2-oxoethoxy]hydroxyphosphinyl]-2-methyl-4-oxo-3-azetidinyl]carbamic acid, 1,1-dimethylethyl ester, monopotassium salt (117 mg, 0.25 mmol) in 2.5 ml of dry dichloromethane was added 100 μl of anisole and the mixture was then cooled to 0° C. in an ice bath under argon. Trifluoroacetic acid (1 ml) was added and the mixture stirred for two hours. The reaction mixture was diluted with 5 ml of dry toluene and the solvents removed in vacuo at room temperature yielding a yellow oily residue. The residue was triturated with hexanes (2×10 ml) followed by trituration with ether (2×10 ml). The solid was dried in vacuo yielding the title compound. |
Here is a chemical reaction formula: Reactants are:m2_m3_m4:C1(=CC=C(C=C1)S(=O)(=O)O)C;m2_m3_m4:O=C1C=C(NC=C1OCC1=CC=CC=C1)C(OC)O;m2_m3_m4:C(C)OC(C=P(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=O, Reagents are:, and Products are 0:O=C1C=C(NC=C1OCC1=CC=CC=C1)/C=C/C(=O)OCC;0:C1(=CC=CC=C1)P(C1=CC=CC=C1)(C1=CC=CC=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: p-Toluenesulfonic acid (0.5 g), 6.26 g of 1,4-dihydro-4-oxo-2-[(hydroxy)(methoxy)methyl]-5-(phenylmethoxy)pyridine and 8.35 g of (triphenylphosphoranylidene)acetic acid ethyl ester were stirred for three hours at 70° C. A clear dark solution was formed. Evaporation of the solvent in vacuo yielded an oily residue of the title compound and triphenylphosphine oxide. This was dissolved in 30 ml of isopropanol. After standing overnight in a refrigerator, the resulting crystals were filtered off, washed with ether and recrystallized from isopropanol (yield: 5.72 g). |