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Here is a chemical reaction formula: Reactants are:m2_m4:[H-].[Al+3].[Li+].[H-].[H-].[H-];m1_m3:C(C)OC(=O)C=1C(=NC(=NC1)SC)NC, Reagents are:m2_m4:O1CCCC1;m1_m3:O1CCCC1, and Products are 0:CNC1=NC(=NC=C1CO)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 4-methylamino-2-methylsulfanyl-5-pyrimidinecarboxylate ethyl ester (4.36 g, 19.3 mmol) in 60 mL of tetrahydrofuran was added dropwise to a room temperature suspension of lithium aluminum hydride (1.10 g, 29.0 mmol) in 40 mL of tetrahydrofuran. After 10 minutes the reaction was carefully quenched with 2 mL of water, 2 mL of 15% NaOH, and an additional 7 mL of water. The mixture was stirred for 1 hour, and the white precipitate which had formed was removed by filtration, and was washed with ethyl acetate. The filtrate was concentrated in vacuo and 3:1 hexane:ethyl acetate was added. The solids were collected to give 2.99 g (84%) of 4-methylamino-2-methylsulfanyl-5-pyrimidinemethanol; mp 155°-157° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:CNC1=NC(=NC=C1CO)SC;m1_m4_m2_m5:O.O.[Cr](=O)(=O)([O-])O[Cr](=O)(=O)[O-].[Na+].[Na+];m3_m6:O.O.[Cr](=O)(=O)([O-])O[Cr](=O)(=O)[O-].[Na+].[Na+], Reagents are:m1_m4_m2_m5:C(C)(=O)O;m1_m4_m2_m5:C(C)(=O)O;m3_m6:C(C)(=O)O, and Products are 0:CNC1=NC(=NC=C1C=O)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Methylamino-2-methylsulfanyl-5-pyrimidine-methanol (2.40 g, 13.0 mmol) in 7 mL of acetic acid was added to a solution of sodium dichromate-dihydrate (1.30 g, 4.4 mmol) in 6 mL of acetic acid. After 2 hours at room temperature, additional sodium dichromate-dihydrate (0.3 g, 1.0 mmol) in 1 mL of acetic acid was added. After a total reaction time of 3.5 hours, the bright yellow solid was removed by filtration. Water (30 mL) was added to the filtrate, followed by aqueous ammonium hydroxide until basic (pH 9.0). The mixture was cooled in the refrigerator for 30 minutes. The precipitate was collected and dissolved in ethyl acetate, and the solution was dried over MgSO4. Filtration and concentration in vacuo gave 0.72 g (30%) of 4-methylamino-2-methylsulfanyl-5-pyrimidinecarboxaldehyde; mp 99°-101° C. |
Here is a chemical reaction formula: Reactants are:m4:C(C)(=O)OCC;m1_m2_m3_m5:C([O-])([O-])=O.[K+].[K+];m1_m2_m3_m5:CNC1=NC(=NC=C1C=O)SC;m1_m2_m3_m5:ClC1=C(C(=CC=C1)Cl)CC#N;m1_m2_m3_m5:CN(C=O)C, Reagents are:m6:C(Cl)Cl, and Products are 0:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)SC)N(C1=N)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Powdered potassium carbonate (0.8 g; 5.8 mmol) was added to a solution of 0.220 g (1.2 mmol) of the aldehyde from Example 18 and 0.235 g (1.26 mmol) (ca. 5% excess) of 2,6-dichlorophenylacetonitrile in 2.0 mL of dimethylformamide. The mixture was heated with stirring at 125° C. for 6 hours. Ethyl acetate (5 mL) was added to the cooled mixture, and the solids were filtered and washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residual gum was triturated with 10 mL of water, and the resulting solid was filtered, washed well with water, and dried. This crude material was chromatographed by placing a chloroform solution on a silica gel column wet with chloroform. The column was eluted with 1:1 (v/v) hexane:ethyl acetate, collecting the fractions that contain the Rf 0.25 spot on tlc (1:1 hexane:ethyl acetate). Evaporation of the solvents gave a solid. The solid product was dissolved in about 0.5 mL of methylene chloride. Crystals develop. Petroleum ether (ca. 2 mL) was added, and the crystals were filtered to provide 0.168 g (40%) of 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-ylideneamine, mp 198°-200° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)OCCOCC)N(C1=N)C, Reagents are:m1_m2:Cl, and Products are 0:Cl.ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)O)N(C1=N)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 78.0 mg (0.20 mmol) of the ethoxyethyl ether from Example 22 in 1.0 mL of 6N hydrochloric acid was heated at reflux for 5 minutes. The solvent was removed by evaporation under reduced pressure. The remaining solid hydrochloride salt was recrystallized from ethanol-ethyl acetate to afford crystalline 6-(2,6-dichlorophenyl)-2-hydroxy-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-ylideneamine, hydrochloride; mp 255°-260° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=O)C;m1_m2_m3:COC=1C=CC(=CC1)P2(=S)SP(=S)(S2)C=3C=CC(=CC3)OC, Reagents are:m1_m2_m3:N1=CC=CC=C1, and Products are 0:NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=S)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 0.321 g (1.0 mmol) of 2-amino-6-(2,6-dichlorophenyl)-8-methyl-pyrido[2,3-d]pyrimidin-7-(8H)-one from Example 12 and 0.404 g (1.0 mmol) of Lawesson's Reagent in 10 mL of pyridine was heated at reflux with stirring for 24 hours. The solvent was evaporated under reduced pressure, and the residue was triturated with 20 mL of water, filtered, and the cake washed well with water. Purification was by silica gel chromatography to afford the desired compound identified as 2-amino-6-(2,6-dichlorophenyl)-8-methyl-pyrido[2,3-d]-pyrimidin-7(8H)-thione. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)SC)N(C1=O)C;m1_m2_m3:C(C1=CC=CC=C1)N, Reagents are:m1_m2_m3:CN(C=O)C, and Products are 0:C(C1=CC=CC=C1)NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 0.165 g (0.47 mmol) of 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido-[2,3-d]pyrimidin-7-one of Example 37, 0.50 g (4.70 mmol) of benzylamine and 0.5 mL of dimethylformamide was heated with stirring in a 120° C. oil bath. After 5 minutes, solution was complete. After 5 hours, the excess amine and dimethylformamide were evaporated at reduced pressure, and the residue was triturated with a solution of 1 mL of acetone and 2 mL of petroleum ether. The tacky solid was filtered and recrystallized from ethyl acetate/petroleum ether to give 0.092 g of pure product; mp 217°-219° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)SC)N(C1=O)C;m1_m2_m3:NCC1=NC=CC=C1, Reagents are:m1_m2_m3:CN(C=O)C, and Products are 0:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NCC2=NC=CC=C2)N(C1=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 0.165 g (0.47 mmol) of 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one of Example 37, 1.08 g (10.0 mmol) of 2-(aminomethyl)pyridine and 0.5 mL of dimethylformamide was heated with stirring in a 130° C. oil bath. After 2 minutes, solution was complete. After 2 hours, the excess amine and dimethylformamide were evaporated at reduced pressure. Ether (5 mL) was added to the residue. Crystals immediately developed. Water (5 mL) was added, and the entire mixture was filtered. The cake was washed 5 mL of ether, 5 mL of water, and then dried; wt 0.164 g. Recrystallization from ethyl acetate gave 0.075 g of pure product; mp 198°-201° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:[OH-].[Na+];m1_m2:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NC2=CC=C(C=C2)CCCC(=O)OCC)N(C1=O)C, Reagents are:m3:C(C)(=O)O, and Products are 0:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NC2=CC=C(C=C2)CCCC(=O)O)N(C1=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A volume of 5 mL of 2N sodium hydroxide was added to a hot stirred solution of 0.170 g (0.33 mmol) of 4-[4-{6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-phenyl}-butyric acid, ethyl ester of Example 91. The solution was maintained at reflux for 1 hour. Glacial acetic acid (1 mL) was added, and the reaction solution was evaporated to ca. 25 mL volume. Water (50 mL) was added to precipitate a solid. The mixture was filtered, and the cake was washed well with water and dried; wt 0.130 g. Hydrolysis did not go to completion under these conditions. The product was purified to remove starting ester by silica gel chromatography eluting with 1:20 methanol:chloroform to obtain 55 mg of pure acid; mp 169°-171° C. |
Here is a chemical reaction formula: Reactants are:m1_m3:C(C)OC(=O)C=1C(=NC(=NC1)SC)NCC;m2_m4:[H-].[Al+3].[Li+].[H-].[H-].[H-], Reagents are:m1_m3:O1CCCC1;m2_m4:O1CCCC1, and Products are 0:C(C)NC1=NC(=NC=C1CO)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 4-ethylamino-2-methylthio-5-pyrimidinecarboxylate ethyl ester (8.93 g, 37.1 mmol) in 100 mL of tetrahydrofuran was added dropwise to a room temperature suspension of lithium aluminum hydride (2.30 g, 60.5 mmol) in 100 mL of tetrahydrofuran. After 10 minutes, the reaction was carefully quenched with 4.5 mL of water, 4.5 mL of 15% NaOH, and 16 mL of water, and the mixture was stirred for 1.5 hours. The white precipitate was removed by filtration washing with ethyl acetate. The filtrate was concentrated in vacuo and 1:1 hexane:ethyl acetate was added. The solids were collected to give 6.77 g (92%) of 4-ethylamino-2-methylthio-5-pyrimidinemethanol; mp 152°-156° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)NC1=NC(=NC=C1CO)SC, Reagents are:m4:[O-2].[Mn+2];m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[Mn+2], and Products are 0:C(C)NC1=NC(=NC=C1C=O)SC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 4-ethylamino-2-methylthio-5-pyrimidinemethanol (6.44 g, 32.4 mmol) in 600 mL of chloroform was added manganese oxide (21.0 g, 241 mmol) over 3 minutes. The suspension was stirred at room temperature for 2 hours, and an additional 5.5 g of manganese oxide was added. Stirring was continued for 4.5 hours. The mixture was then filtered through celite washing with chloroform. The filtrate was concentrated in vacuo to give 6.25 g (97%) of 4-ethylamino-2-methylthio-5-formylpyrimidine; mp 58°-61° C. |
Here is a chemical reaction formula: Reactants are:m1_m4:C(C)OC(=O)C=1C(=NC(=NC1)NC1=CC=CC=C1)NCC;m2_m5:[H-].[Al+3].[Li+].[H-].[H-].[H-];m3:[H-].[Al+3].[Li+].[H-].[H-].[H-], Reagents are:m1_m4:O1CCCC1;m2_m5:O1CCCC1, and Products are 0:C(C)NC1=NC(=NC=C1CO)NC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 4-ethylamino-2-phenylamino-pyrimidine-5-carboxylic acid ethyl ester (109 mg, 0.38 mmol) in 6 mL of tetrahydrofuran was added dropwise to a room temperature suspension of lithium aluminum hydride (35 mg, 0.92 mmol) in 5 mL of tetrahydrofuran. After 25 minutes, an additional 30 mg of lithium aluminum hydride was added, and stirring was continued for 30 minutes. The reaction was carefully quenched with 120 μL of water, 200 μL of 15% NaOH, and 300 μL of water. After stirring for 1 hour, the white precipitate was removed by filtration washing with ethyl acetate. The filtrate was concentrated in vacuo, and the crude material was purified by flash chromatography eluting with ethyl acetate to provide 36 mg (39%) of (4-ethylamino-2-phenylamino-pyrimidin-5-yl)methanol; mp 174°-176° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)NC1=NC(=NC=C1CO)NC1=CC=CC=C1, Reagents are:m1_m2_m3:C(Cl)(Cl)Cl;m1_m2_m3:[O-2].[Mn+2], and Products are 0:C(C)NC1=NC(=NC=C1C=O)NC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of (4-ethylamino-2-phenylamino-pyrimidin-5-yl)methanol (173 mg, 0.71 mmol) in 15 mL of chloroform was added manganese oxide (600 mg, 6.89 mmol). After stirring at room temperature overnight, the mixture was filtered through a pad of Celite, washing with chloroform. The filtrate was concentrated in vacuo to give 170 mg (99%) of 4-ethylamino-2-phenylamino-pyrimidine-5-carbaldehyde; mp 155°-157° C. |
Here is a chemical reaction formula: Reactants are:m3:C(C)NC1=NC(=NC=C1C=O)NC1=CC=CC=C1;m2:S1C=C(C=C1)CC#N;m4:O;m1_m5:[H-].[Na+], Reagents are:m1_m5:C(C)OCCO, and Products are 0:C(C)N1C(C(=CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CSC=C2)=N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 27 mg) in 5 mL of 2-ethoxyethanol was added 3-thiopheneacetonitrile (168 mg, 1.36 mmol). After stirring for 5 minutes at room temperature, 4-ethylamino-2-phenylamino-pyrimidine-5-carbaldehyde (300 mg, 1.24 mmol) was added, and the reaction heated at 120° C. for 2 hours, resulting in a dark brown solution. Upon cooling, the solution was poured into water which caused precipitation. The resulting precipitate was removed by filtration and washed with water. The crude product was purified by flash chromatography, eluting with 5% methanol/methylene chloride, followed by 10% methanol/methylene chloride. Concentration of product fractions yielded 340 mg (78%) of (8-ethyl-7-imino-6-thiophen-3-yl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine; mp 220°-222° C. |
Here is a chemical reaction formula: Reactants are:m4:O;m3:C(C)NC1=NC(=NC=C1C=O)NC1=CC=CC=C1;m1_m5:[H-].[Na+];m2:S1C(=CC=C1)CC#N, Reagents are:m1_m5:C(C)OCCO, and Products are 0:C(C)N1C(C(=CC2=C1N=C(N=C2)NC2=CC=CC=C2)C=2SC=CC2)=N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 27 mg) in 5 mL of 2-ethoxyethanol was added 2-thiopheneacetonitrile (168 mg, 1.36 mmol). After stirring for 5 minutes at room temperature, 4-ethylamino-2-phenylamino-pyrimidine-5-carbaldehyde (300 mg, 1.24 mmol) was added, and the reaction heated at 120° C. for 2 hours, resulting in a dark brown solution. Upon cooling, the solution was poured into water which caused precipitation. The resulting precipitate was removed by filtration and washed with water. The crude product was purified by flash chromatography, eluting with 5% methanol/methylene chloride, followed by 10% methanol/methylene chloride. Concentration of product fractions yielded 370 mg (85%) of (8-ethyl-7-imino-6-thiophen-2-yl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine; mp 204°-205° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=N)CC;m1_m2:C(C)(=O)OC(C)=O;m3:Cl, Reagents are:m4:O, and Products are 0:BrC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (6-(2-Bromo-6-chlorophenyl)-8-ethyl-7-imino-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine (150 mg) was added to 1 mL of acetic anhydride and heated at reflux for 5 minutes. The reaction was cooled and concentrated resulting in an oil which was heated at reflux with 10 mL of 6N HCl for 10 minutes. The reaction was cooled, and 30 mL of water was added causing precipitation. The precipitate was removed by filtration and washed with water. The resulting solid was dried to give 130 mg of 6-(2-bromo-6-chlorophenyl)-8-ethyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one; mp softens at 195° C. and melts at 210°-214° C. |
Here is a chemical reaction formula: Reactants are:m3:C(C)OCC;m1_m4_m2:C(C)(C)(C)OC(CN1C(C(=CC2=C1N=C(N=C2)N)C2=C(C=CC=C2Cl)Cl)=O)=O;m1_m4_m2:FC(C(=O)O)(F)F, Reagents are:m1_m4_m2:C(Cl)Cl, and Products are 0:NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=O)CC(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of [2-amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-yl]-acetic acid tert-butyl ester (157 mg, 0.37 mmol) from Example 36 in 4 mL of methylene chloride was added 2 mL of trifluoroacetic acid. The solution was stirred at room temperature for 5 hours, then concentrated in vacuo. The resultant oil was partitioned between methylene chloride and brine. The aqueous layer was washed with ethyl acetate, and the organic layers were combined, dried over magnesium sulfate, filtered, and concentrated in vacuo to give a gummy solid. Diethyl ether was added, and the resultant precipitate was collected. Hexane was added to the filtrate, and once again the resultant precipitate was collected. The solids were combined and dried in vacuo at 80° C. to give 71 mg (52%) of [2-amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-yl]-acetic acid that was >97% pure by HPLC; mp 297°-300° C. dec. |
Here is a chemical reaction formula: Reactants are:m3:BrCC1=C(C=CC=C1Cl)Cl;m1_m4:[H-].[Na+];m2:NC=1N=CC2=C(N1)NC(C(=C2)C2=C(C=CC=C2Cl)Cl)=O, Reagents are:m1_m4:CN(C=O)C, and Products are 0:NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=O)CC2=C(C=CC=C2Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 36 mg) in 8 mL of dimethylformamide was added 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one (208 mg, 0.68 mmol). The mixture was heated at 70° C. for 10 minutes and then at 50° C. for 30 minutes, resulting in a clear solution. α-Bromo-2,6-dichlorotoluene (215 mg, 0.90 mmol) was added, and the reaction mixture was heated at 50° C. for 25 minutes, then poured onto ice water. The resulting precipitate was removed by filtration and washed with water. The solid was purified by flash chromatography, eluting with 1:1 hexane:ethyl acetate then dried in vacuo to provide 112 mg (35%) of 2-amino-8-(2,6-dichlorobenzyl)-6-(2,6-dichlorophenyl)-8H-pyrido[2,3-d]pyrimidin-7-one; mp 274°-276° C. |
Here is a chemical reaction formula: Reactants are:m2:NC=1N=CC2=C(N1)NC(C(=C2)C2=C(C=CC=C2Cl)Cl)=O;m3:ClCCCC1=CC=CC=C1;m1_m4:[H-].[Na+], Reagents are:m5:C(C)(=O)OCC;m1_m4:CN(C=O)C, and Products are 0:NC=1N=CC2=C(N1)N(C(C(=C2)C2=C(C=CC=C2Cl)Cl)=O)CCCC2=CC=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 58 mg) in 10 mL of dimethylformamide was added 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one (320 mg, 1.04 mmol). The mixture was heated to 60° C. resulting in a clear solution. 1-Chloro-3-phenylpropane (260 μL, 1.81 mmol) was added, and the reaction mixture was heated at 60° C. for 35 minutes, then poured onto ice water. The resulting gummy solid was dissolved in ethyl acetate, washed with water, and dried over magnesium sulfate. Filtration, followed by concentration in vacuo, gave an oil that was purified by flash chromatography, eluting with 1:3 hexane:ethyl acetate to provide 345 mg of crude product. Recrystallization from ethyl acetate and hexane followed by drying in vacuo provided 253 mg (57%) of 2-amino-6-(2,6-dichlorophenyl)-8-(3-phenylpropyl)-8H-pyrido[2,3-d]pyrimidin-7-one; mp 161°-163° C. |
Here is a chemical reaction formula: Reactants are:m2:C1=C(C=CC2=CC=CC=C12)CC#N;m1_m5:[H-].[Na+];m4:O;m3:C(C)NC1=NC(=NC=C1C=O)NC1=CC=CC=C1, Reagents are:m1_m5:C(C)OCCO, and Products are 0:C(C)N1C(C(=CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC1=CC=CC=C1C=C2)=N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 27 mg) in 5 mL of 2-ethoxyethanol was added 2-naphthyl-acetonitrile (227 mg, 1.36 mmol). After stirring for 5 minutes at room temperature, 4-ethylamino-2-phenylamino-pyrimidine-5-carbaldehyde (300 mg, 1.24 mmol) was added and the reaction heated at 110° C. for 1 hour, resulting in a dark brown solution. Upon cooling, the solution was poured into 30 mL of water which caused precipitation. The resulting precipitate was removed by filtration and washed with water. The crude product was purified by flash chromatography, eluting with 5% methanol/methylene chloride, followed by 10% methanol/methylene chloride. Concentration of product fractions yielded 400 mg (82%) of yellow solid, (8-ethyl-7-imino-6-naphthalen-2-yl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine; mp 236°-242° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C)N1C(C(=CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC1=CC=CC=C1C=C2)=N;m1_m2:C(C)(=O)OC(C)=O;m3:Cl, Reagents are:m4:O, and Products are 0:C(C)N1C(C(=CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC1=CC=CC=C1C=C2)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (8-Ethyl-7-imino-6-naphthalen-2-yl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine (150 mg) was added to 1 mL of acetic anhydride and heated at reflux for 2 minutes. The reaction was cooled and concentrated, resulting in an oil which was heated at reflux with 10 mL of 6N HCl for 10 minutes. The reaction was cooled, and 40 mL of water was added causing precipitation. The precipitate was removed by filtration and washed with water. The resulting solid was dried in a vacuum oven to provide 8-ethyl-6-naphthalen-2-yl-2-phenylamino-8H-pyrido[2,3-d]-pyrimidin-7-one; mp 254°-256° C. |
Here is a chemical reaction formula: Reactants are:m3:Cl.ClCC1=NC=CC=C1;m1_m2_m4:N1C(=S)NC(=O)C1;m1_m2_m4:C[O-].[Na+], Reagents are:m1_m2_m4:CO, and Products are 0:N1=C(C=CC=C1)CSC=1NCC(N1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 1 g of 2-thiohydantoin and 2.5 g of sodium methylate were dissolved in 50 mL of methanol (MeoH), and 1.5 g of 2-chloromethylpyridine hydrochloride was added to the solution. The reaction mixture was stirred under reflux for one and a half hour and concentrated in vacuo. To the residue, there was added 50 mL of chloroform (CHCl3), and the mixture was washed with 50 mL of water. Then, the CHCL3 layer was dried over magnesium sulfate (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography [using a developing solvent consisting of CHCl3 :MeOH=50:1 (volume ratio, v/v)]. Recrystallization from diethylether gave the desired compound in the form of a needle-like crystal. The yield of this compound was 1.2 g with a yield ratio of 67.2%, and its melting point was 105°-107° C. |
Here is a chemical reaction formula: Reactants are:m4:[OH-].[Na+];m1_m5:CC1(C(NC(N1)=S)=O)C;m2:Cl.CN(C1=C(CCl)C=CC=C1)C;m3:O, Reagents are:m1_m5:CS(=O)C, and Products are 0:CN(C1=C(CSC=2NC(C(N2)=O)(C)C)C=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 1 g of 5,5-dimethyl-2-thiohydantoin was dissolved in 20 mL of dimethylsulfoxide, and 1.7 g of 2-dimethylaminobenzylchloride hydrochloride was added to the solution. The reaction mixture was stirred at the room temperature for one hour, and poured into 50 mL of water. The pH value of the solution was adjusted to 7-8 with diluted aqueous solution of 2N sodium hydroxide (NaOH). A precipitated sediment was extracted from the liquid, two times, using 50 mL of ethyl acetate (AcOEt). The AcOEt layer was successively washed with 50 mL of water and 50 mL of brine, dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The thus obtained residue was purified by column chromatography [developing solvent=CHCl3 :MeOH=20:1 (volume ratio, v/v)]. Recrystallized from diethyl ether gave the desired compound in the form of needle-like crystal. The yield of the compound was 1.2 g with a yield ratio of 62.4%, and its melting point was 113°-115° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:Cl.CN(C1=C(CCl)C=CC=C1)C;m1_m2_m4:C(C)(=O)N1C(=S)NC(=O)C1(C)C;m3:[OH-].[Na+], Reagents are:m5:O, and Products are 0:C(C)(=O)N1C(=NC(C1(C)C)=O)SCC1=C(C=CC=C1)N(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 4.18g of 2-dimethylaminobenzylchloride hydrochloride was added to a solution of 3.43 g of 1-N-acetyl-5,5-dimethyl-2-thiohydantoin in 50 mL of N,N-dimethylsulfoxide. The reaction mixture was stirred for one hour at the room temperature and poured into 100 mL of water. The pH of the solution was adjusted to 7-8 with a diluted aqueous solution of NaOH and extracted. The precipitate was extracted with 100 mL of ethyl acetate (AcOEt). The thus obtained AcOET layer was successively washed two times with 100 mL of water and 100 mL of brine, dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The thus obtained residue was purified by column chromatography (using CHCL3 as a developing solvent). Recrystallized from diethyl ether-n-hexane gave the desired compound in the form of needle-like crystal. The yield of this compound was 3.4 g with a yield ratio of 57.6%, and the melting point was 99°-100° C. |
Here is a chemical reaction formula: Reactants are:m1:Cl.CN(C1=C(CCl)C=CC=C1)C;m2:C(C)(=O)N1C(=S)NC(=O)C1(C)CC, Reagents are:, and Products are 0:C(C)(=O)N1C(=NC(C1(C)CC)=O)SCC1=C(C=CC=C1)N(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In the present Example, 2.27 g of 2-dimethylaminobenzylchloride hydrochloride and 2.0 g of 1-N-acetyl-5-ethyl-5-methyl-2-thiohydantoin were reacted following the procedure of Example 33. The desired compound was obtained in the form of needle-like crystal. The yield of this compound was 1.37 g with a yield ratio of 41.1%, and the melting point was 83°-85° C. |
Here is a chemical reaction formula: Reactants are:m3:CI;m4_m6:C(C)(=O)OCC;m1_m5_m2:CN(C1=C(CSC=2NC(C(N2)=O)(C)C)C=CC=C1)C;m1_m5_m2:[H-].[Na+], Reagents are:m4_m6:O;m1_m5_m2:CN(C=O)C, and Products are 0:CN1C(=NC(C1=O)(C)C)SCC1=C(C=CC=C1)N(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 0.5 g of 2-(2-dimethylaminobenzylthio)-5,5-dimethylimidazolin-4-one in 20 mL of N,N-dimethylformamide, there was added 60% sodium hydride in 0.09 g of mineral oil at -10° C. After the mixture was stirred for 15 minutes, 1 mL of methyl iodide was added to the mixture, and the stirring was continued for one hour. To the reaction mixture, there were added 100 mL of ethyl acetate (AcOEt) and 100 mL of water. The AcOEt layer was separated. The separated AcOEt layer was washed three times with 50 mL of brine, dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The residue was purified by column chromatography (using CHCl3 as a developing solvent), to give the desired compound in the form of a syrup. The yield of this compound was 0.41 g with a yield ratio of 78.1%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:Cl.CN(C1=C(CCl)C=CC=C1)C;m1_m2_m3:CC1(C(NC(N1)=O)=S)C, Reagents are:m1_m2_m3:CO, and Products are 0:CN(C1=C(CSC2=NC(NC2(C)C)=O)C=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 2.5 g of 2-dimethylaminobenzylchloride hydrochloride was added to a solution of 1.5 g of 5,5-dimethyl-4-thiohydantoin in 50 mL of methanol (MeQH). The reaction mixture was stirred for two hours at the room temperature and concentrated in vacuo. To the residue, there was added 100 mL of CHCl3. The residue was washed two times with 100 mL of aqueous solution of NaHCO3, dried over MgSO4 and concentrated in vacuo. The residue purified by column chromatography [CHCl3 :MeOH=100:1 (v/v)]. Recrystallized from diethyl ether gave the desired compound in the form of needle-like crystal. The yield of this compound was 2 g with a yield ratio of 69.1%, and the melting point was 160°-162° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:CN(C1=C(CSC2=NC(NC2(C)C)=O)C=CC=C1)C;m1_m2:CI, Reagents are:, and Products are 0:CN1C(N=C(C1(C)C)SCC1=C(C=CC=C1)N(C)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 0.5 g of 4-(2-dimethylaminobenzylthio)-5,5-dimethyl-3-imidazolin-2-one was reacted with 1 mL of methyl iodide following the procedure used in Example 35. The desired compound was obtained in the form of a syrup. The yield of this compound was 0.43 g with a yield ratio of 81.9%. A result of a 1 H-NMR analysis of the compound is as follows: |
Here is a chemical reaction formula: Reactants are:m1:Cl.CN(C1=C(CCl)C=CC=C1)C;m2:C(C)C1(C(NC(N1)=O)=S)C, Reagents are:, and Products are 0:CN(C1=C(CSC2=NC(NC2(C)CC)=O)C=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In the present Example, 2.3 g of 2-dimethylaminobenzylchloride hydrochloride and 1.5 g of 5-ethyl-5-methyl-4-thiohydantoin were reacted following the procedure used in Example 36. Crystallization from diethyl ether-n-hexane gave the desired compound in the form of a needle-like crystal. The yield of this compound was 1.9 g with a yield ratio of 68.6%, and the melting point was 111°-113° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:Cl.CN(C1=C(CCl)C=CC=C1)C;m1_m3_m2_m4:CC1(C(NC(N1)=S)=S)C, Reagents are:m1_m3_m2_m4:CCO;m1_m3_m2_m4:C(C)O, and Products are 0:CN(C1=C(CSC2=NC(C(=N2)SCC2=C(C=CC=C2)N(C)C)(C)C)C=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, a solution of 9.1 g of 2-dimethylaminobenzylchloride hydrochloride in 50 mL of EtOH was added to a solution of 7 g of 5,5-dimethyl-2,4-dithiohydantoin in 100 mL of ethanol (EtOH). The reaction mixture was stirred for 1.5 hour at the room temperature and concentrated in vacuo. To the residue, there was added 100 mL of chloroform (CHCl3). The residue was then washed with an aqueous solution of potassium carbonate (CaCO3), dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The residue was chromatographed on a column of silica gel (CHCl3). From the earlier fractions, 2,4-bis(2-dimethylaminobenzylthio)-5,5-dimethyl-5H-imidazole was isolated as a syrup. The yield of this compound was 1.1 g with a yield ratio of 5.9%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:Cl.CN(C=1C=C(CCl)C=CC1)C;m1_m2_m3_m4:CC1(C(NC(N1)=S)=S)C;m1_m2_m3_m4:C[O-].[Na+], Reagents are:m1_m2_m3_m4:CO, and Products are 0:CN(C=1C=C(CSC2=NC(C(=N2)SCC2=CC(=CC=C2)N(C)C)(C)C)C=CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 2.94 g of 3-dimethylaminobenzylchloride hydrochloride was added to a mixture of 1.6 g of 5,5-dimethyl-2,4-dithiohydantoin and 1.3 g of sodium methoxide in 50 mL of methanol (MeOH). The reaction mixture was stirred at the room temperature for one hour, and concentrated in vacuo. The residue was treated following the procedure used in Example 56, and chromatographed on a column of silica gel (CHCl3). From the earlier fractions, 2,4-bis(3-dimethylaminobenzylthio)-5,5-dimethyl-5H-imidazole was isolated, in the form of a syrup. The yield of this compound was 0.31 g with a yield ratio of 7.4%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrCC=1C=CC=C2C=CC=NC12;m1_m2_m3:CC1(C(NC(N1)=S)=S)C, Reagents are:m1_m2_m3:C(C)O, and Products are 0:N1=CC=CC2=CC=CC(=C12)CSC1=NC(C(=N1)SCC=1C=CC=C2C=CC=NC12)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 3 g of 8-bromomethylquinoline was added to a solution of 1 g of 5,5-dimethyl-2,4-dithiohydantoin in 50 mL of ethanol (EtOH). The reaction mixture was stirred at the room temperature for 1.5 hour, and concentrated in vacuo. To the residue, 100 mL of CHCl3 was added. The mixture was washed with an aqueous solution of K2CO3, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatograph (CHCl3). Recrystallization from diethyl ether gave the desired compound in the form of a needle-like crystal. The yield of this compound was 2.3 g with a yield ratio of 83.3%, and the melting point was 101°-104° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:Cl.CN(C=1C=C(CCl)C=CC1)C;m1_m2_m3_m4:CC1(C(NC(N1)=S)=S)C;m1_m2_m3_m4:C[O-].[Na+], Reagents are:m1_m2_m3_m4:CO, and Products are 0:CN(C=1C=C(CSC2=NC(C(=N2)SCC2=CC(=CC=C2)N(C)C)(C)C)C=CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 3.1 g of 3-dimethylaminobenzylchloride hydrochloride was added to a mixture of 0.8 g of 5,5-dimethyl-2,4-dithiohydantoin and 1.34 g of sodium methoxide in 50 mL of methanol (MeOH). The reaction mixture was treated following the procedure used in Example 56, and purified by column chromatograph (CHCl3) to give the desired compound in the form of a syrup. The yield of this compound was 1.65 g with a yield ratio of 82.9%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:Cl.CN(C1=CC=C(CCl)C=C1)C;m1_m2_m3:CC1(C(NC(N1)=S)=S)C, Reagents are:m1_m2_m3:C(C)O, and Products are 0:CN(C1=CC=C(CSC2=NC(C(=N2)SCC2=CC=C(C=C2)N(C)C)(C)C)C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 3.2 g of 4-dimethylaminobenzylchloride hydrochloride was added to a solution of 1 g of 5,5-dimethyl-2,4-dithiohydantoin in 50 mL of ethanol (EtOH). The reaction mixture was treated following the procedure used in Example 62, and purified by column chromatography (CHCl3). Recrystallization form diethyl ether-n-hexane gave the desired compound in the form of a needle-like crystal. The yield of this compound was 1.9 g with a yield ratio of 71.2%, and the melting point was 91°-92° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C1=CC=CC=C1)Br;m1_m2_m3:CC1(C(NC(N1)=S)=S)C, Reagents are:m1_m2_m3:C(C)O, and Products are 0:C(C1=CC=CC=C1)SC=1NC(C(N1)=S)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 1.91 mL of benzylbromide was added to a solution of 1.6 g of 5,5-dimethyl-2,4-dithiohydantoin in 50 mL of ethanol (EtOH). The reaction mixture was stirred at the room temperature for one hour, and concentrated in vacuo. The residue was treated following the procedure used in Example 62, and purified by column chromatography (CHCl3). Recrystallization from diethyl ether-n-hexane gave 2-benzylthio-5,5-dimethylimidazolin-4-thione in the form of a needle-like crystal. The yield of this compound was 0.87 g with a yield ratio of 34.8%, and the melting point was 133°-134° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:Cl.CN(C1=C(CCl)C=CC=C1)C;m1_m2_m3:C(C1=CC=CC=C1)SC=1NC(C(N1)=S)(C)C, Reagents are:m1_m2_m3:C(C)O, and Products are 0:C(C1=CC=CC=C1)SC1=NC(C(=N1)SCC1=C(C=CC=C1)N(C)C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Initially, 0.65 g of 2-dimethylaminobenzylchloride hydrochloride was added to a solution of 0.7 g of 2-benzylthio-5,5-dimethylimidazolin-4-thione in 20 mL of ethanol (EtOH). The reaction mixture was stirred at the room temperature for one hour, and concentrated in vacuo. The residue was treated following the procedure used in Example 62, and purified by column chromatography (CHCl3). Recrystallization from diethyl ether-n-hexane gave 2-benzylthio-4-(2-dimethylaminobenzylthio)-5,5-dimethyl-5H-imidazole in the form of a needle-like crystal. The yield of this compound was 0.75 g with a yield ratio of 72.2%, and the melting point was 91°-92° C. |
Here is a chemical reaction formula: Reactants are:m4:C1(=CC=CC=C1)C;m3:FC(C(=O)O)(F)F;m1_m2_m5:C(C)(C)(C)OC(C(CC(C)C)NC(C1=C(C=C(C=C1)OC)SSC1=C(C=CC(=C1)OC)C(NC(CC(C)C)C(=O)OC(C)(C)C)=O)=O)=O;m1_m2_m5:C1(=CC=CC=C1)OC, Reagents are:m1_m2_m5:ClCCl, and Products are 0:C(=O)(O)C(CC(C)C)NC(=O)C1=C(C=C(C=C1)OC)SSC1=C(C(=O)NC(C(=O)O)CC(C)C)C=CC(=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of [S-(R*,R*)-2[2-[2-(1-tert-butoxycarbonyl-3-methyl-butylcarbamoyl)-5-methoxyphenyldisulfanyl]-4-methoxybenzoylamino]-4-methyl-pentanoic acid tert-butyl ester (1.2 g, 1.7 mmol) and anisole (1 mL) in 10 mL dichloromethane, cooled to about 0° C., was treated dropwise with 10 mL of trifluoroacetic acid. The mixture was allowed to warm to ambient temperature. After 4 hours, 5 mL toluene was added, and the solvents were removed in vacuo. The crude product was recrystallized from methanol/water to yield 0.7 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m1:C(C)(C)(C)OC(C(CC(C)C)N(C(C1=CC=CC(=C1)F)=O)SSC1=C(C=C(C=C1)F)C(NC(CC(C)C)C(=O)OC(C)(C)C)=O)=O;m2:FC(C(=O)O)(F)F, Reagents are:m3:ClCCl;m4:C1(=CC=CC=C1)OC, and Products are 0:C(=O)(O)C(CC(C)C)NC(=O)C1=C(C=CC(=C1)F)SSC1=C(C(=O)NC(C(=O)O)CC(C)C)C=C(C=C1)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The general method of Preparation 20 was followed using [S-(R*,R*)]-2-[2-[[2-(1-tert-butoxycarbonyl-3-methyl-butylcarbamoyl)-4-fluorophenyldisulfanyl]-5-fluorobenzoylamino]-4-methyl pentanoic acid tert-butyl ester (1.8 g, 2.6 mmol) in 20 mL dichloromethane, anisole (2 mL), and 20 mL trifluoroacetic acid. The crude product was recrystallized from methanol/water to afford 0.9 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m2:FC(C(=O)O)(F)F;m1:C(C)(C)(C)OC(C(CC(C)C)NC(C1=C(C=C(C=C1)C)SSC1=C(C=CC(=C1)C)C(NC(CC(C)C)C(=O)OC(C)(C)C)=O)=O)=O, Reagents are:m3:ClCCl;m4:C1(=CC=CC=C1)OC, and Products are 0:C(=O)(O)C(CC(C)C)NC(=O)S(SC1=C(C(=O)NC(C(=O)O)CC(C)C)C=CC(=C1)C)C1=CC=CC(=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The general method of Preparation 20 was followed using [S-(R*,R*)]-2-[2-[2-(1-tert-butoxycarbonyl-3-methyl-butylcarbamoyl)-5-methyl-phenyldisulfanyl]-4-methyl-benzoylamino]-4-methyl-pentanoic acid tert-butyl ester (1.9 g, 2.8 mmol) in 20 mL dichloromethane, anisole (2.0 mL), and 10 mL trifluoroacetic acid. The crude product was recrystallized from methanol/water to yield 1.1 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m1:C(C)(C)(C)OC(C(CC(C)C)NC(=O)C=1C(=NC=CC1)SSC1=NC=CC=C1C(NC(CC(C)C)C(=O)OC(C)(C)C)=O)=O;m2:FC(C(=O)O)(F)F, Reagents are:m4:C1(=CC=CC=C1)OC;m3:ClCCl, and Products are 0:C(=O)(O)C(CC(C)C)NC(=O)C=1C(=NC=CC1)SSC1=NC=CC=C1C(=O)NC(C(=O)O)CC(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The general method of Preparation 20 was followed using [S-(R*,R*)]-2-([2-[3-(1-tert-butoxycarbonyl-3-methyl-butylcarbamoyl)-pyridin-2-yldisulfanyl]pyridine-3-carbonyl]-amino)-4-methyl-pentanoic acid tert-butyl ester (1.9 g, 2.9 mmol) in 20 mL dichloromethane, anisole (1.5 mL), and 10 mL trifluoroacetic acid. The crude product was recrystallized from methanol/water to yield 1.2 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:C(C1=C(C=CC=C1)SSC1=C(C(=O)Cl)C=CC=C1)(=O)Cl;m1_m3_m2_m4:C(C)(=O)NS(=O)(=O)C1=CC=C(N)C=C1, Reagents are:m1_m3_m2_m4:ClCCl;m1_m3_m2_m4:N1=CC=CC=C1, and Products are 0:C(C)(=O)NS(=O)(=O)C1=CC=C(C=C1)NC(C1=C(C=CC=C1)SSC1=C(C(=O)NC2=CC=C(C=C2)S(=O)(=O)NC(C)=O)C=CC=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The compound was prepared according to the general method of Preparation 9 using 2,2'-dithiobisbenzoyl chloride (3.0 g, 8.0 mmol) in 30 mL of dichloromethane and 4-[(acetylamino) sulfonyl]aniline (5.6 g, 26.0 mmol) in 100 mL of pyridine. The crude product was purified on a silica gel column using chloroform/methanol (1:1 v/v) as the mobile phase. The pure fractions were pooled, concentrated in vacuo, and the solid was crystallized from ethanol/water (1:1 v/v) to yield 0.5 g of the title compound, mp 180°-182° C. |
Here is a chemical reaction formula: Reactants are:m1:N[C@@H](C(C)C)C(=O)O;m2:C(C1=C(C=CC=C1)SSC1=C(C(=O)Cl)C=CC=C1)(=O)Cl, Reagents are:, and Products are 0:C(=O)(O)C(C(C)C)NC(=O)C1=C(C=CC=C1)SSC1=C(C(=O)NC(C(=O)O)C(C)C)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the method employed in Preparation 30, 17.8 g (0.15 mol) of D,L valine was reacted with 17.2 g (0.05 mol) of 2,2'-dithiobisbenzoyl chloride to produce 11.4 g of the title compound after recrystallization from acetic acid, mp 226.5°-227.5° C. |
Here is a chemical reaction formula: Reactants are:m2:C(C1=C(C=CC=C1)SSC1=C(C(=O)Cl)C=CC=C1)(=O)Cl;m1:NCCCC(=O)O, Reagents are:, and Products are 0:C(=O)(O)CCCNC(=O)C1=C(C=CC=C1)SSC1=C(C(=O)NCCCC(=O)O)C=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the procedure in Preparation 30, 16 g (0.15 mol) of 4-amino-butanoic acid was reacted with 10.8 g (0.03 mol) of 2,2'-dithiobisbenzoyl chloride to afford 7.14 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m1:C(C)N(CCNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)Cl)CC;m2:S.[Na], Reagents are:, and Products are 0:C(C)N(CCNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S)CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure in Preparation 34, 6.4 g (0.02 mol) of 4-chloro-2-phenyl-pyrimidine-5-carboxylic acid (2-diethylamino-ethyl)-amide was reacted with 4.8 g (0.066 mol) of sodium hydrogen sulfide to afford 4.2 g of the title compound, mp 178°-180° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)N(C)C)Cl;m1_m2:S.[Na], Reagents are:, and Products are 0:C(C1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)N(C)C)S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Preparation 34, 14.3 g (0.045 mol) of 4-chloro-2-dimethylamino-pyrimidine-5-carboxylic acid benzylamide and 12 g (0.21 mol) of sodium hydrogen sulfide were reacted to give 5.7 g of the title compound, mp 175°-178° C. |
Here is a chemical reaction formula: Reactants are:m2:S.[Na];m1:C(C1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)Cl, Reagents are:, and Products are 0:C(C1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure from Preparation 34, 5.8 g (17.9 mmol) of 4-chloro-2-phenyl-pyrimidine-5-carboxylic acid benzylamide was reacted with 5.1 g (72 mmol) of sodium hydrogen sulfide to give 3.75 g of the title compound, mp 189°-193° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m4_m2_m5:C(=O)(O)C(CC(C)C)NC(=O)C1=C(C=CC(=C1)F)SSN(C(C(=O)O)CC(C)C)C(C1=CC=CC(=C1)F)=O;m1_m3_m4_m2_m5:BrBr, Reagents are:m1_m3_m4_m2_m5:C(C)#N;m1_m3_m4_m2_m5:ClCCl;m1_m3_m4_m2_m5:ClCCl, and Products are 0:CC(C[C@@H](C(=O)O)N1SC2=C(C1=O)C=C(C=C2)F)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the general method of Example 3, a slurry of {s-(R*,R*)]-2-{-[2-(1-carboxy-3-methylbutylcarbamoyl)-4-fluorophenyldisulfanyl]-5-fluorobenzoylamino}-4-methyl-pentanoic acid (2.1 g, 3.6 mmol) (from Preparation 21) in 8 mL acetonitrile and 25 mL dichloromethane was treated with bromine (0.7 g, 4.4 mmol) in 15 mL dichloromethane. The crude compound was recrystallized from methanol/water to afford 1.4 g of the title compound, mp 161°-162° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m4_m2_m5:C(=O)(O)C(CC(C)C)NC(=O)C1=C(C=CC(=C1)C)SSN(C(C(=O)O)CC(C)C)C(C1=CC=CC(=C1)C)=O;m1_m3_m4_m2_m5:BrBr;m1_m3_m4_m2_m5:C(C)#N, Reagents are:m1_m3_m4_m2_m5:ClCCl;m1_m3_m4_m2_m5:ClCCl, and Products are 0:CC(C[C@@H](C(=O)O)N1SC2=C(C1=O)C=CC(=C2)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the general method of Example 3, a slurry of [s-(R*,R*)]-2-[-[2-(1-carboxy-3-methylbutylcarbamoyl)-4-methylphenyldisulfanyl]-5-methylbenzoylamino]-4-methyl-pentanoic acid (1.8 g, 3.2 mmol) (from Preparation 22) in 5 mL acetonitrile and 20 mL dichloromethane was reacted with bromine (0.6 g, 3.7 mmol) in 10 mL dichloromethane. The crude product was recrystallized from methanol/water to afford 1.3 g of the title compound. |
Here is a chemical reaction formula: Reactants are:m1:C(=O)(O)C(CC(C)C)NC(=O)C1=C(C=CC=C1)SSC1=C(C(=O)NC(C(=O)O)C(C)C)C=CC=C1;m2:BrBr, Reagents are:, and Products are 0:CC(C(C(=O)O)N1SC2=C(C1=O)C=CC=C2)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the procedure of Example 13, 6.0 g (13.6 mol) of 2-[2-[2-(1-carboxy-3-methylbutyl carbamoyl)phenyldisulfanyl]benzoylamino]-3-methylbutanoic acid was reacted with bromine to provide 2.25 g of the title compound, mp 166°-168° C. |
Here is a chemical reaction formula: Reactants are:m2:ClSC1=C(C(=O)Cl)C=CC=C1;m1:NC1=NC=CC(=C1)C, Reagents are:m3:N1=CC=CC=C1, and Products are 0:CC1=CC(=NC=C1)N1SC2=C(C1=O)C=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the method of Fischer and Hurni (Arzneimittel Forsch., 1964;14:1301) 5.4 g (0.05 mol) of 2-amino-4-methylpyridine in 50 mL of pyridine at 10° C. was reacted with 10.3 g (0.05 mol) of 2-chlorosulfenylbenzoyl chloride. The mixture was heated to 50° C. and maintained at that temperature for 2 hours. The mixture was cooled to 25° C. and filtered. The solid was recrystallized from benzene to give 4.5 g of the title compound, mp 195°-196.5° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:NC1=CC=C(C=C1)CC(=O)O;m1_m2_m4:C(C)N(CC)CC;m3:ClSC1=C(C(=O)Cl)C=CC=C1, Reagents are:m1_m2_m4:CCOCCO, and Products are 0:O=C1N(SC2=C1C=CC=C2)C2=CC=C(C=C2)CC(=O)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 7.55 g (0.05 mol) of 4-aminophenylacetic acid and 15.15 g (0.15 mol) of triethylamine in 25 mL of ethyl cellosolve was added 10.3 g (0.05 mol) of 2-chlorosulfenylbenzoyl chloride (Arzneimittel Forsch., 1964;14:1301). The mixture was stirred at room temperature for 3 hours, concentrated in vacuo, and water was added to the residue. The mixture was acidified with HCl and filtered to give 9.9 g of the title compound, mp 173°-175° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4_m3_m5:N1=C(C=CC=C1)CCNC(=O)C=1C=NC=2C=C3C(=CC2C1S)OCO3;m1_m2_m4_m3_m5:C(C)N(CC)CC;m1_m2_m4_m3_m5:II, Reagents are:m1_m2_m4_m3_m5:CO;m1_m2_m4_m3_m5:CO, and Products are 0:N1=C(C=CC=C1)CCN1SC2=C(C=NC=3C=C4C(=CC23)OCO4)C1=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 4.1 g (0.012 mol) of 8-mercapto-[1,3]dioxolo [4,5-g]quinoline-7-carboxylic acid (2-pyridin-2-yl-ethyl)-amide (from Preparation 34) and 5 mL (0.035 mol) of triethylamine in 750 mL of methanol was added 2.95 g (0.012 mol) of iodine in 100 mL of methanol. The mixture was heated at reflux for 2 hours, cooled, and then concentrated to an oil. The residue was slurried in water, and the solid was collected and recrystallized in ethanol to give 3.5 g of the title compound, mp 200°-201° C. |
Here is a chemical reaction formula: Reactants are:m2:II;m1:C(C)N(CCNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S)CC, Reagents are:, and Products are 0:C(C)N(CCN1SC2=NC(=NC=C2C1=O)C1=CC=CC=C1)CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 3.3 g (0.01 mol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid (2-diethylamino-ethyl)-amide (from Preparation 36) and 2.54 g (0.01 mol) of iodine were reacted to give 2.25 g of the title compound after recrystallization from isopropanol, mp 106°-107° C. |
Here is a chemical reaction formula: Reactants are:m2:II;m1:C(C1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S, Reagents are:, and Products are 0:C(C1=CC=CC=C1)N1SC2=NC(=NC=C2C1=O)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 2.0 g (6.22 mmol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid benzylamide (from Preparation 42) was reacted with 1.74 g (6.8 mmol) of iodine to give 1.74 g of the title compound after crystallization from isopropanol, mp 166°-167° C. |
Here is a chemical reaction formula: Reactants are:m1:N1(CCOCC1)CCNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S;m2:II, Reagents are:, and Products are 0:N1(CCOCC1)CCN1SC2=NC(=NC=C2C1=O)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 2.0 g (5.81 mmol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide were treated with 1.47 g (5.81 mmol) of iodine to give 1.21 g of the title compound after recrystallization from isopropanol, mp 163°-165° C. |
Here is a chemical reaction formula: Reactants are:m1:C(CC1=CC=CC=C1)NC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S;m2:II, Reagents are:, and Products are 0:C(CC1=CC=CC=C1)N1SC2=NC(=NC=C2C1=O)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 2.0 g (5.96 mmol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid phenethyl-amide were treated with 1.66 g (6.56 mmol) of iodine to give 1.42 g of the title compound after recrystallization from isopropanol, mp 144°-147° C. |
Here is a chemical reaction formula: Reactants are:m1:N1=C(C=CC=C1)CNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S;m2:II, Reagents are:, and Products are 0:C1(=CC=CC=C1)C1=NC=C2C(=N1)SN(C2=O)CC2=NC=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 2.0 g (6.20 mmol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid (pyridin-2-ylmethyl)-amide were treated with 1.73 g (6.82 mmol) of iodine to give 1.62 g of the title compound after recrystallization from isopropanol, mp 154°-156° C. |
Here is a chemical reaction formula: Reactants are:m2:II;m1:N1=C(C=CC=C1)CCNC(=O)C=1C(=NC(=NC1)C1=CC=CC=C1)S, Reagents are:, and Products are 0:C1(=CC=CC=C1)C1=NC=C2C(=N1)SN(C2=O)CCC2=NC=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 14.0 g (41.6 mmol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide were treated with 10.6 g (41.7 mmol) of iodine to give 12.7 g of the title compound after recrystallization from ethanol, mp 132°-133° C. |
Here is a chemical reaction formula: Reactants are:m1:N1=C(C=CC=C1)CCNC(=O)C=1C(=NC(=NC1)N1CCCCC1)S;m2:II, Reagents are:, and Products are 0:N1(CCCCC1)C1=NC=C2C(=N1)SN(C2=O)CCC2=NC=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 33.0 g (96.2 mmol) of 4-mercapto-2-piperidin-1-yl-pyrimidine-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide were treated with 24.4 g (96.1 mmol) of iodine to give 21.4 g of the title compound after recrystallization from aqueous ethanol, mp 109°-110° C. |
Here is a chemical reaction formula: Reactants are:m1:SC1=NC(=NC=C1C(=O)N)N1CCCCC1;m2:II, Reagents are:, and Products are 0:N1(CCCCC1)C1=NC=C2C(=N1)SNC2=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 20.8 g (87.4 mmol) of 4-mercapto-2-piperidin-1-yl-pyrimidine-5-carboxylic acid amide were treated with 22.2 g (87.4 mmol) of iodine to give 14.37 g of the title compound after recrystallization from dimethylformamide, mp 268°-269° C. |
Here is a chemical reaction formula: Reactants are:m2:II;m1:N1(CCCCC1)CCNC(=O)C=1C(=NC(=NC1)N1CCOCC1)S, Reagents are:, and Products are 0:N1(CCOCC1)C1=NC=C2C(=N1)SN(C2=O)CCN2CCCCC2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 5.2 g (14.8 mmol) of 4-mercapto-2-morpholin-4-yl-pyrimidine-5-carboxylic acid (2-piperidin-1-yl-ethyl)-amide were treated with 3.81 g (15.0 mmol) of iodine to give 2.6 g of the title compound after recrystallization from aqueous isopropanol, mp 98°-100° C. |
Here is a chemical reaction formula: Reactants are:m1:N1=C(C=CC=C1)CCNC(=O)C=1C(=NC(=NC1)N(C)C)S;m2:II, Reagents are:, and Products are 0:CN(C1=NC=C2C(=N1)SN(C2=O)CCC2=NC=CC=C2)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 7.5 g (24.8 mmol) of 2-dimethylamino-4-mercapto-pyrimidine-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide were treated with 6.4 g (25.2 mmol) of iodine to give 4.21 g of the title compound after recrystallization from isopropanol, mp 134°-136° C. |
Here is a chemical reaction formula: Reactants are:m2:II;m1:N1(CCCCC1)CCNC(=O)C=1C(=NC(=NC1)N(C)C)S, Reagents are:, and Products are 0:CN(C1=NC=C2C(=N1)SN(C2=O)CCN2CCCCC2)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure of Example 20, 6.2 g (20.1 mmol) of 2-dimethylamino-4-mercapto-pyrimidine-5-carboxylic acid (2-piperidin-1-yl-ethyl)-amide were treated with 5.08 g (20.0 mmol) of iodine to give 5.31 g of the title compound after recrystallization from ethyl acetate, mp 128°-129° C. |
Here is a chemical reaction formula: Reactants are:m2:CC(C)=NO;m3:C(CCC)[Li];m1:COC(=O)C12CCCN2CCC1, Reagents are:, and Products are 0:CC1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-(Methoxycarbonyl)-hexahydro-1H-pyrrolizine (from step 1d, 1.56 g, 9.22 mmol), acetone oxime (1.45 g, 19.8 mmol) and n-butyllithium (2.5M in hexane, 16 mL, 39.6 mmol) were combined in a similar fashion as that outlined by J. Saunders et at., J. Med. Chem. 1990, 33: 1128. The crude material was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford a yellow oil (199 mg, 11%). MS (CI/NH3) m/e: 193 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.76-1.92 (m, 6H), 2.14-2.29 (m, 2H), 2.24 (s, 3H), 2.61-2.69 (m, 2H), 3.13-3.32 (m, 2H), 5.95 (s, 1H). |
Here is a chemical reaction formula: Reactants are:m2_m3:CCOCC;m2_m3:Cl;m1_m4:N1=CC(=CC=C1)C12CCCN2CCC1, Reagents are:m1_m4:C(Cl)Cl, and Products are 0:Cl.N1=CC(=CC=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 3a, 125 mg, 0.66 mmol) was dissolved in CH2Cl2 (15 mL) and Et2O saturated with HCl (g) was added dropwise. The solvent was removed, and the remaining solid was triturated with CH2Cl2 (2×) to afford a hygroscopic yellow solid (140 mg, 81%). MS (CI/NH3) m/e: 189 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.13-2.29 (m, 2H), 2.32-2.43 (m, 2H), 2.48-2.69 (m, 4H), 3.40-3.49 (m, 2H), 3.83-3.92 (m, 2H), 7.92 (dd, J=8.5, 5.5 Hz, 1H), 8.43 (ddd, J=8.5, 2.6, 1.4 Hz, 1H), 8.75 (dd, J=5.5, 1.4 Hz, 1H), 8.88 (d, J=2.6 Hz, 1H). Anal. Calcd for C12H18Cl2N2.0.5H2O: C, 53.34; H, 7.09; N, 10.37. Found: C, 53.28; H, 6.96; N, 10.22. |
Here is a chemical reaction formula: Reactants are:m1_m5_m2_m6:[Li]CCCC;m1_m5_m2_m6:BrC=1C=NC2=CC=CC=C2C1;m4:Cl;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12, Reagents are:m1_m5_m2_m6:C1CCOC1;m7:CCOC(=O)C, and Products are 0:N1=CC(=CC2=CC=CC=C12)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 2.5M nBuLi (1.2 mL, 2.8 mmol) in hexanes was added to 3-bromoquinoline (386 μL, 2.8 mmol) in THF (10 mL) at -100° C. followed immediately by 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (200 mg, 0.9 mmol). The reaction mixture was allowed to stir for 2 hours at -100° C. and then 2N HCl was added at 0° C. After warming to ambient temperature, the mixture was poured over EtOAc and the phases were separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (3×). The organic fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; EtOAc) to afford a pale solid (104 mg, 46%). mp 80°-83° C. MS (CI/NH3) m/e: 239 (M+H)+. 1 H NMR (CDCl3, 300 MHz) δ1.61-1.75 (m, 2H), 1.83-1.94 (m, 2H), 2.03-2.17 (m, 4H), 2.71-2.80 (m, 2H), 3.20-3.27 (m, 2H), 7.52 (ddd, J=7.0, 7.0, 1.1 Hz, 1H), 7.65 (ddd, J=7.0, 7.0, 1.5 Hz, 1H), 7.82 (d, J=8.1 Hz, 1H), 8.05 (d, J=8.5 Hz, 1H), 8.32 (d, J=2.2, Hz, 1H), 8.97 (d, J=2.2 Hz, 1H). |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:ClC1=CC=C(C=N1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.ClC1=CC=C(C=N1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(6-Chloro-3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 5a, 210 mg, 0.94 mmol) was dissolved in Et2O (8 mL), and Et2O saturated with HCl (g) was added at ambient temperature. Solvent was then removed, and the remaining solid was recrystallized from MeOH/Et2O to afford short white needles (189 mg, 78%). mp 141°-143° C. MS (CI/NH3) m/e: 223 (M+H)+. 1H NMR D2O, 300 MHz) δ2.12-2.50 (m, 6H), 2.58-2.65 (m, 2H), 3.33-3.42 (m, 2H), 3.69-3.88 (m, 2H), 7.62 (d, J=8.5 Hz, 1HO, 7.99 (dd, J=8.5, 2.7 Hz, 1H), 8.53 (d, J=2.7 Hz, 1H). Anal. Calcd for C12H16Cl2N2 : C, 55.61; H, 6.22; N, 10.81. Found: C, 55.10; H, 6.36; N, 10.57. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:FC1=NC=CC=C1C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.FC1=NC=CC=C1C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(2-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 6a, 59 mg, 0.3 mmol) was dissolved in Et2O (8 mL), and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was recrystallized from MeOH/Et2O to afford a white solid (54 mg, 77%). mp 185°-186° C. MS (CI/NH3) m/e: 207 (M+H)+. 1H NMR D2O, 300 MHz) a 2.06-2.21 (m, 2H), 2.27-2.41 (m, 4H), 2.65-2.77 (m, 2H), 3.32-3.40 (m, 2H), 3.85-3.95 (m, 2H), 7.47 (ddd, J=7.7, 4.8, 1.8 Hz, 1H), 8.14 (ddd, J=10.7, 7.7, 1.8 Hz, 1H), 8.27 (ddd, J=4.8, 1.8, 1.1 Hz, 1H). Anal. Calcd for C12H16ClFN2 : C, 59.38; H, 6.64; N, 11.54. Found: C, 59.14; H, 6.53; N, 11.34. |
Here is a chemical reaction formula: Reactants are:m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m4:Cl;m1_m5_m2_m6:[Li]C(C)(C)C;m1_m5_m2_m6:ClC1=NC=C(C=C1Cl)I, Reagents are:m1_m5_m2_m6:CCCCC;m1_m5_m2_m6:CCOCC, and Products are 0:ClC=1C=C(C=NC1Cl)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 1.7M tBuLi (4.7 mL, 8.0 mmol) in pentane was added to 2,3-dichloro-5-iodopyridine (from step 8a, 1.0 g, 3.65 mmol) in Et2O (15 mL) precooled to -100° C. After stirring for 2 minutes, 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (1.5 g, 7.3 mmol) was added, and the reaction mixture was allowed to stir for 20 minutes at -100° C. then gradually warm to -20° C. A solution of 2N HCl was added, and the cold bath was removed. After warming to ambient temperature, the reaction mixture was poured over EtOAc and the phases were separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5) to afford a light yellow oil (510 mg, 54%). MS (CI/NH3) m/e: 257 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.80-2.08 (m, 6H), 2.64-2.72 (m, 2H), 3.11-3.20 (m, 2H), 7.99 (d, J=2.2 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H). |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1:ClC=1C=C(C=NC1Cl)C12CCCN2CCC1, Reagents are:m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.ClC=1C=C(C=NC1Cl)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 8b, 128 mg, 0.50 mmol) was slurried in Et2O (8 mL), and Et2O saturated with HCl (g) added. The solvent was removed, and the solid was recrystallized from MeOH/Et2O to afford a white solid (111 mg, 75%). mp 215°-217° C. MS (CI/NH3) m/e: 257 (M+H)+. 1H NMR D2O, 300 MHz) δ2.12-2.50 (m, 6H), 2.54-2.65 (m, 2H), 3.35-3.43 (m, 2H), 3.79-3.88 (m, 2H), 8.21 (d, J=2.4 Hz, 1H), 8.47 (d, J=2.4 Hz, 1H). Anal. Calcd for C12H15C13N2 : C, 49.09; H, 5.15; N, 9.54. Found: C, 49.01; H, 5.15; N, 9.44. |
Here is a chemical reaction formula: Reactants are:m4:Cl;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m1_m5_m2_m6:[Li]C(C)(C)C;m1_m5_m2_m6:BrC=1C=NC=NC1, Reagents are:m7:CCOCC;m1_m5_m2_m6:CCCCC;m1_m5_m2_m6:CCOCC.C1CCOC1, and Products are 0:N1=CN=CC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 1.7M tBuLi (1.6 mL, 2.6 mmol) in pentane was added to 5-bromopyrimidine (190 mg, 1.2 mmol) in Et2O:THF (1:1, 12 mL) at -100° C. After stirring for 10 minutes, 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.4 mmol) was added to the reaction slurry, and stirring was continued for 30 minutes. The reaction mixture was then allowed to warm to 0° C. and stir for 1 hour. A solution of 2N HCl was added, and the reaction mixture was poured over Et2O and the phases separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (40 mg, 18%). MS (CI/NH3) m/e: 190 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.60-1.73 (m, 2H), 1.82-2.11 (m, 6H), 2.66-2.75 (m, 2H), 3.15-3.21 (m, 2H), 8.85 (s, 2H), 9.05 (s,1H). |
Here is a chemical reaction formula: Reactants are:m1_m5_m2_m6:[Li]CCCC;m1_m5_m2_m6:C(C)(C)NC(C)C;m3:FC1=NC(=CC=C1)F;m4:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12, Reagents are:m1_m5_m2_m6:C1CCOC1, and Products are 0:FC1=NC(=CC=C1C12CCCN2CCC1)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.6 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-difluoropyridine (145 μL, 1.6 mmol) was introduced, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.4 mmol) was then added, and the cold bath was removed. After warming to ambient temperature, a solution of 2N HCl was added and the phases were separated after pouting the reaction mixture over EtOAc. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 extracts were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (180 mg, 50%). MS (CI/NH3) m/e: 225 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.5-1.63 (m, 2H), 1.78-1.89 (m, 2H), 1.92-2.10 (m, 4H), 2.63-2.70 (m, 2H), 3.08-3.12 (m, 2H), 6.72 (dd, J=8.1, 3.0 Hz, 1H), 8.33 (dd, J=18.0, 8.1 Hz, 1H). |
Here is a chemical reaction formula: Reactants are:m4_m1_m2_m3:Cl;m4_m1_m2_m3:FC1=NC(=CC=C1C12CCCN2CCC1)F, Reagents are:m4_m1_m2_m3:CCOCC;m4_m1_m2_m3:CCOCC, and Products are 0:Cl.FC1=NC(=CC=C1C12CCCN2CCC1)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of Et2O saturated with HCl (g) was added to 7a-(2,6-difluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 10a, 174 mg, 0.8 mmol) in Et2O (10 mL). The slurry was filtered, and the filter cake was washed with Et2O to afford a white solid (138 mg, 68%). mp 205°-206° C. MS (CI/NH3) m/e: 225 (M+H)+. 1H NMR D2O, 300 MHz) δ2.08-2.21 (m, 2H), 2.26-2.40 (m, 4H), 2.64-2.73 (m, 2H), 3.31-3.40 (m, 2H), 3.82-3.90 (m, 2H), 7.14 (dd, J=8.5, 2.7 Hz, 1H), 8.22-8.30 (m, 1H). Anal. Calcd for C12H15 ClF2N2 : C, 54.92; H, 5.70; N, 10.52. Found: C, 55.28; H, 5.80; N, 10.74 |
Here is a chemical reaction formula: Reactants are:m4:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m5:Cl;m3:ClC1=NC(=CC=C1)Cl;m1_m6_m2_m7:[Li]CCCC;m1_m6_m2_m7:C(C)(C)NC(C)C, Reagents are:m8:CCOC(=O)C;m1_m6_m2_m7:C1CCOC1, and Products are 0:ClC1=NC(=CC=C1C12CCCN2CCC1)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.7 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-dichloropyridine (237 μL, 1.60 mmol) was added neat, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.40 mmol) was added, and the reaction mixture was allowed to stir for 2 hours at -78° C. then warm to ambient temperature. A solution of 2N HCl was added, and the mixture was then poured over EtOAc. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (70.6 mg, 17%). MS (CI/NH3) m/e: 257/259 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.47-1.61 (m, 2H), 1.77-1.90 (m, 2H), 2.10-2.25 (m, 4H), 2.67-2.75 (m, 2H), 3.03-3.11 (m, 2H), 7.19 (d, J=8.5 Hz, 1H), 8.37 (d, J=8.5 Hz, 1H). |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:ClC1=NC(=CC=C1C12CCCN2CCC1)Cl, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.ClC1=NC(=CC=C1C12CCCN2CCC1)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine (from step 11a, 62 mg, 0.24 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was triturated with Et2O to give a white solid (35.6 mg). mp 212°-214° C. 1H NMR D2O, 300 MHz) δ2.02-2.18 (m, 2H), 2.28-2.41 (m, 2H), 2.52-2.64 (m, 2H), 2.72-2.83 (m, 2H), 3.41-3.50 (m, 2H), 3.92-4.02 (m, 2H), 7.60 (d, J=8.5 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H); MS (ClfNH3) m/z: 257/259 (M+H)+. Anal. Calcd for C12 H16ClFN2 : C, 49.26; H, 4.82; N, 9.57. Found: C, 49.14; H, 5.03; N, 9.47. |
Here is a chemical reaction formula: Reactants are:m1_m4:FC1=NC=C(C=C1)I;m2_m5:[Li]C(C)(C)C;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12, Reagents are:m1_m4:CCOCC;m2_m5:CCCCC, and Products are 0:FC1=CC=C(C=N1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Fluoro-5-iodopyridine (200 μL, 0.90 mmol) was dissolved in Et2O and cooled to -78° C. A solution of 2.5M t-BuLi (1.2 mL, 1.98 mmol) in pentane was added, and the reaction was stirred for 2 minutes. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (375 mg, 1.80 mmol) was added, and the reaction mixture was allowed to stir for 10 minutes at -78° C. then allowed to warm to -20° C. The cold bath was removed, 2N HCl was added, and the mixture was extracted with Et2O. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2 Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (75 mg, 40%). 1H NMR (CDCl3, 300 MHz) δ1.58-1.73 (m, 2H), 1.79-2.05 (m, 6H), 2.64-2.73 (m, 2H), 3.12-3.19 (m, 2H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 7.90 (m, 1H), 8.30 (dd, J=1.4, 0.7 Hz, 1H); MS (CI/NH3) m/z: 207 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:FC=1C=C(C=NC1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.FC=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (62 mg, 0.24 mmol, from step 12d) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was triturated with to give a white solid (57.1 mg, 69%). mp 168°-169° C. 1H NMR D2O, 300 MHz) 67 2.13-2.50 (m, 6H), 2.58-2.67 (m, 2H), 3.34-3.42 (m, 2H), 3.78-3.87 (m, 2H), 7.24 (dd, J=8.8, 2.4, Hz, 1H), 8.13 (ddd, J=8.8, 7.2, 2.7 Hz, 1H), 8.36 (dd, J=2.7, 1.4 Hz, 1H); MS (CI/NH3) m/z: 207 (M+H)+. Anal. Calcd for Cl12H16 ClFN2 : C, 59.38; H, 6.64; N, 11.54. Found: C, 59.51; H, 6.52; N, 11.30. |
Here is a chemical reaction formula: Reactants are:m3:[OH-].[Na+];m1_m2_m4:Cl(=O)(=O)(=O)[O-].[CH+]1CCN2CCCC12;m1_m2_m4:C(#C)[Mg]Br, Reagents are:m5:[Cl-].[Na+].O.O;m1_m2_m4:C1CCOC1, and Products are 0:C(#C)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1,2,3,5,6,7-Hexahydropyrrolizinylium perchlorate (1.0 g, 4.8 mmol) was added to a solution of 0.5M ethynylmagnesium bromide (29 mL, 14.3 mmol) in THF at room temperature. The reaction mixture was allowed to stir for 45 minutes, and 15% NaOH solution was added. The slurry was diluted with brine:water (1:1) and extracted with CH2Cl2 (3×). The organic phases were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 90:10) to afford an amber oil (463 mg, 71%): 1H NMR (CDCl3, 300 MHz) δ1.75-2.06 (m, 6H), 2.14-2.23 (m, 2H), 2.33 (s, 1H), 2.53-2.62 (m, 2H), 3.22-3.28 (m, 2H); MS (Cl/NH3) m/z: 136 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:[N+](=O)([O-])CCC;m1_m2_m4:C1(=CC=CC=C1)N=C=O;m3:C(#C)C12CCCN2CCC1, Reagents are:m1_m2_m4:C1=CC=CC=C1, and Products are 0:C(C)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Nitropropane (0.475 mL, 5.29 mmol) and phenylisocyanate (1.0 mL, 9.5 mmol) were dissolved in benzene (10 mL) and added to a flask containing 7a-ethynyl-hexahydro-1H-pyrrolizine (358 mg, 2.65 mmol, from step 13a). The solution was stirred at ambient temperature for 1 hour and at reflux for 5 hours. The mixture was cooled, filtered, concentrated and diluted with EtOAc. The solution was extracted with 6N HCl. The aqueous phase was made basic with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried (MgSO4) and concentrated. The residue was residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford an amber oil (274 mg, 50%). 1H NMR (CDCl3, 300 MHz) δ1.25 (t, J=7.5 Hz, 3H), 1.75-1.92 (m, 6H), 2.15-2.25 (m, 2H), 2.60-2.69 (m, 4H), 3.13-3.20 (m, 2H), 5.98 (s, 1H); MS (CI/NH3) m/z: 207 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3:C(C)C1=NOC(=C1)C12CCCN2CCC1;m4_m2:Cl, Reagents are:m1_m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.C(C)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-ethyl-5-isoxazolyl)-hexahydro-1H-pyrrolizine (265 mg, 1.30 mmol, from step 13b) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was recrystallized from methanol/ethanol to afford the title compound as a white solid: mp 139°-140° C.; 1H NMR D2O, 300 MHz) δ1.23 (t, J=7.5 Hz, 3H), 2.17-2.40 (m, 6H), 2.58-2.75 (m, 4H), 3.29-3.38 (m, 2H), 3.69-3.77 (m, 2H), 6.64 (s, 1H); MS (CI/NH3) m/z: 207 (M+H)+ ; Anal. Calcd for C12H18N2O.HCl: C, 59.38; H, 7.89; N, 11.54. Found: C, 59.44; H, 7.94; N, 11.48. |
Here is a chemical reaction formula: Reactants are:m3:C(#C)C12CCCN2CCC1;m1_m2_m4:[N+](=O)([O-])CCCC;m1_m2_m4:C1(=CC=CC=C1)N=C=O, Reagents are:m1_m2_m4:C1=CC=CC=C1, and Products are 0:C(CC)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Nitrobutane (0.705 mL, 6.66 mmol) and phenylisocyanate (1.50 mL, 13.3 mmol) were dissolved in benzene (13.5 mL) and added to a flask containing 7a-ethynyl-hexahydro-1H-pyrrolizine (450 mg, 3.33 mmol, from step 13a). The solution was stirred at ambient temperature for 1 hour and at reflux for 5 hours. The mixture was cooled, filtered, concentrated and diluted with EtOAc. The solution was extracted with 6N HCl. The aqueous phase was made basic with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried (MgSO4) and concentrated. The residue was residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford an amber oil (392 mg, 53%). 1H NMR (CDCl3, 300 MHz) δ0.97 (t, J=7.5 Hz, 3H), 1.61-1.92 (m, 8H), 2.15-2.26 (m, 2H), 2.55-2.69 (m, 4H), 3.13-3.20 (m, 2H), 5.96 (s, 1H); MS (CI/NH3) m/z: 221 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3:C(CC)C1=NOC(=C1)C12CCCN2CCC1;m4_m2:Cl, Reagents are:m1_m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.C(CC)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-propyl-5-isoxazolyl)-hexahydro-1H-pyrrolizine (265 mg, 1.30 mmol, from step 14a) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was triturated with Et2O and dried to afford the title compound as a free flowing white powder. mp 97°-98° C. MS (NH3 /CI): m/z 207 (M+H+); 1H NMR (D2O, 300 MHz) δ0.92 (t, J=7.5 Hz, 3H), 1.63-1.75 (m, 2H), 2.20-2.40 (m, 6H), 2.59-2.71 (m, 4H), 3.30-3.38 (m, 2H), 3.70-3.78,(m, 2H), 6.65 (s, 1H); MS (CI/NH3) m/z: 221 (M+H)+.Anal. Calcd for C13H20N2O.HCl: C, 59.38; H, 7.89; N, 11.54. Found: C, 59.44; H, 7.94; N, 11.48. |
Here is a chemical reaction formula: Reactants are:m4:Cl;m3_m6:[OH-].[Na+];m1_m2_m5:C(C1=CC=CC=C1)=O;m1_m2_m5:[N+](=O)([O-])C, Reagents are:m1_m2_m5:CO, and Products are 0:C1(=CC=CC=C1)C=C[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: Benzaldehyde (10.0 g, 94.2 mmol) and nitromethane (5.1 mL, 94.2 mmol) were dissolved in MeOH, the solution was cooled to -18° C., and NaOH (3.9 g, 98.9 mmol) in aqueous solution (80 mL) was added while maintaining the temperature below -10° C. The mixture was stirred at 0° C. for 2 hours, then stored at 5° C. overnight. The solution was then poured into stirring acid (200 mL conc. HCl/300 mL H2O). The precipitate was collected, washed, and recrystallized from EtOH to afford the title compound as light orange needles (5.15 g, 37%). |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:C1(=CC=CC=C1)CC[N+](=O)[O-];m1_m2_m4:C1(=CC=CC=C1)N=C=O;m3:C(#C)C12CCCN2CCC1, Reagents are:m1_m2_m4:C1=CC=CC=C1, and Products are 0:C(C1=CC=CC=C1)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Phenylnitroethane (895 mg, 5.92 mmol, from step 15b) and phenylisocyanate (1.3 mL, 11.8 mmol) were dissolved in benzene (12 mL) and added to a flask containing 7a-ethynyl-hexahydro-1H-pyrrolizine (400 mg, 2.96 mmol, from step 13a). The solution was stirred at reflux for 5 hours, cooled and stirred for 48 hours at room temperature. The mixture was filtered and extracted with 6N HCl. The aqueous phase was made basic with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford an amber oil (415 mg, 52%). 1H NMR (CDCl3, 300 MHz) δ1.71-1.92 (m, 6H), 2.11-2.23 (m, 2H), 2.58-2.66 (m, 2H), 3.08-3.15 (m, 2H), 3.95 (s, 2H), 5.87 (s, 1H), 7.20-7.34 (m, 5H); MS (CI/NH3) m/z: 269 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3:C(C1=CC=CC=C1)C1=NOC(=C1)C12CCCN2CCC1;m4_m2:Cl, Reagents are:m1_m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.C(C1=CC=CC=C1)C1=NOC(=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-Benzyl-5-isoxazolyl)-hexahydro-1H-pyrrolizine (407 mg, 1.52 mmol, from step 15c) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the precipitate was recrystallized from MeOH and dried to afford the title compound as white needles: mp 126°-127° C.; 1H NMR D2O, 300 MHz) δ2.17-2.36 (m, 6H), 2.53-2.62 (m, 2H), 3.28-3.36 (m, 2H), 3.67-3.75 (m, 2H), 4.08 (s, 2H), 6.57 (s, 1H), 7.34-7.45 (m, 5H); MS (CI/NH3) m/z: 269 (M+H)+; Anal. Calcd for C17H20N2O.HCl: C, 66.99; H, 6.94; N, 9.19. Found: C, 66.99; H, 6.87; N, 9.09. |
Here is a chemical reaction formula: Reactants are:m1_m5:[H-].[Na+];m4:[NH4+].[Cl-];m2:C(C1=CC=CC=C1)O;m3:BrC=1C=NC=C(C1)Br, Reagents are:m1_m5:CN(C)C=O;m6:O, and Products are 0:C(C1=CC=CC=C1)OC=1C=NC=C(C1)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (60% in mineral oil, 40.9 g, 1.0 mol) in DMF (800 mL) was cooled to 0° C., and benzyl alcohol (105 mL, 1.0 mol) was slowly added. After stirring for 1 hour at ambient temperature, 3,5-dibromopyridine (200.4 g, 846 mmol) was added and the mixture allowed to stir for 16 hours. Saturated NH4Cl solution (500 mL) was added followed by water (400 mL), and the mixture was extracted with Et2O (5×300 mL). The combined Et2O extracts were washed with 50% brine (6×300 mL), dried (MgSO4), concentrated and the residue recrystallized from Et2O to afford a white solid (161 g, 72%): 1H NMR (CDCl3, 300 MHz) δ5.10 (s, 2H), 7.50-7.35 (m, 6H), 8.37-8.27 (m, 2H); MS (CI/NH3) m/z: 264/266 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m1_m4:C(C1=CC=CC=C1)OC=1C=NC=C(C1)Br;m2_m5:[Li]C(C)(C)C, Reagents are:m1_m4:CCOCC;m2_m5:CCCCC, and Products are 0:C(C1=CC=CC=C1)OC=1C=NC=C(C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 3-Benzyloxy-5-bromopyridine (1.18 g, 4.47 mmol) was dissolved in Et2O and cooled to -78° C. A solution of 2.5M t-BuLi (5.8 mL, 9.83 mmol) in pentane was added, and the reaction was stirred for 10 minutes. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (1.4 g, 6.70 mmol) was added, and the reaction mixture was allowed to stir for 3 hours at -78° C. then allowed to warm to -20° C. and stir for 2 hours. The cold bath was removed, 2N HCl was added, and the mixture was extracted with Et2O. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (286 mg, 22%): mp 45°-49° C. 1H NMR (CDCl3, 300 MHz) δ1.58-1.69 (m, 2H), 1.78-1.83 (m, 2H), 1.89-2.03 (m, 4H), 2.63-2.72 (m, 2H), 3.05-3.18 (m, 2H), 5.12 (s, 2H), 7.31-7.54 (m, 6H), 8.17 (d, J=3.0 Hz, 1H), 8.29 (d, J=1.7 Hz, 1H); MS (CI/NH3) m/z: 295 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C1=CC=CC=C1)OC=1C=NC=C(C1)C12CCCN2CCC1, Reagents are:m1_m2:CO;m3:[Pt], and Products are 0:OC=1C=NC=C(C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-Benzyloxy-5-pyridinyl)-hexahydro-1H-pyrrolizine (260 mg, 0.88 mmol, from step 16b) was dissolved in methanol (9 mL), 10% Pt/C (35 mg) was added, and the mixture stirred under 1 arm of H2 for 16 hours. The catalyst was removed, the filtrate was concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH/0.5 % NH4OH, 90:10:0 to 90:10:0.5) to afford the title compound as a white solid (114 mg, 63%). 1H NMR D2O, 300 MHz) δ2.07-2.40 (m, 6H), 2.49-2.58 (m, 2H), 3.26-3.34 (m, 2H), 3.71-3.80 (m, 2H), 7.00 (dd, J=2.4, 2.0 Hz, 1H), 7.80 (d, J=2.0 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H): MS (CI/NH3) m/z: 205 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m2_m3:CCOCC;m2_m3:Cl;m1_m4:OC=1C=NC=C(C1)C12CCCN2CCC1, Reagents are:m1_m4:C(Cl)Cl, and Products are 0:Cl.OC=1C=NC=C(C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(3-Hydroxy-5-pyridinyl)-hexahydro-1H-pyrrolizine (150 mg, 0.56 mmol, from step 16c) was dissolved in methylene chloride, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was dried to afford the title compound as a white powder (114 mg, 91%): mp 175°-180° C. (dec.); 1H NMR D2O, 300 MHz) δ2.11-2.63 (m, 8H), 3.35-3.44 (m, 2H), 3.80-3.89 (m, 2H), 7.66 (dd, J=2.4, 2.0 Hz, 1H), 8.23 (d, J=2.4 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H); MS (CI/NH3) m/z: 205 (M+H)+. Anal. Calcd for C12H16N2O.HCl: C, 53.40; H, 6.65; N, 10.38. Found: C, 53.55; H, 6.62; N, 10.24. |
Here is a chemical reaction formula: Reactants are:m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m2_m4:[Li]C(C)(C)C;m1:BrC=1C=NC=C(C1)Br, Reagents are:m2_m4:CCCCC, and Products are 0:BrC=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 3,5-dibromopyridine (500 mg, 2.11 mmol, Aldrich) was dissolved in Et2 O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 2.7 mL, 4.64 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (663 mg, 3.2 mmol) was added, and the reaction mixture was allowed to stir and warm to -10° C. and stir for 2 hours. The cold bath was removed, 2N HCl was added, and the phases were separated. The aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2 Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (160 mg, 28%): 1H NMR (CDCl3, 300 MHz) 67 1.57-1.71 (m, 2H), 1.79-2.04 (m, 6H), 2.62-2.73 (m, 2H), 3.11-3.20 (m, 2H), 8.04 (dd, J=2.0, 2.0 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H); MS (CI/NH3) m/z: 267/269 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m4:BrC=1C=C(C=NC1)C12CCCN2CCC1;m2_m3:CCOCC;m2_m3:Cl, Reagents are:m1_m4:C(Cl)Cl, and Products are 0:Cl.BrC=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5-bromo-3-pyridinyl)-hexahydro-1H-pyrrolizine (107 mg, 0.52 mmol, from step 16c) was dissolved in methylene chloride, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound as an off-white powder (118 mg). mp 192°-194° C. 1H NMR D2O, 300 MHz) δ2.13-2.51 (m, 6H), 2.57-2.66 (m, 2H), 3.36-3.44 (m, 2H), 3.81-3.89(m, 2H), 8.22 (s, 1H), 8.65 (s, 1H), 8.72 (s, 1H); MS (CI/NH3) m/z: 267/269 (M+H)+. Anal. Calcd for C12 H15BrN2.HCl: C, 47.47; H, 5.31; N, 9.23. Found: C, 47.40; H, 5.22; N, 8.98. |
Here is a chemical reaction formula: Reactants are:m2:[F-].[K+];m1:ClC1=NC=C(C=C1C)[N+](=O)[O-], Reagents are:m4:C(C)#N;m5:CCOCC;m3:[Br-].C1(=CC=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1, and Products are 0:FC1=NC=C(C=C1C)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.), KF (12 g, 258 mmol) and tetraphenylphosphonium bromide (20 g, 47.7 mmol; Aldrich) were combined in 200 mL of acetonitrile and heated at reflux for 4 days. The mixture was diluted with Et2O (500 mL) and filtered, and the filtrate was concentrated. The residue was triturated with hot hexane (4×200 mL), and the hexane solutions were combined and concentrated to afford the title compound as a solid (8.4 g, 60%): 1H NMR (DMSO-d6, 300 MHz) δ2.42 (s, 3H), 8.43 (m, 1H), 8.95 (dd, J=1.6 Hz, 1H); MS (CI/NH3) m/z: 157 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:FC1=NC=C(C=C1C)[N+](=O)[O-], Reagents are:m1_m3_m2:CCO;m1_m3_m2:[Pd], and Products are 0:NC=1C=C(C(=NC1)F)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Fluoro-3-methyl-5-nitropyridine (8.2 g, mmol) was combined with 5% Pd/C (100 mg) in EtOH (100 mL) under a H2 atmosphere for 16 hours. The mixture was filtered and concentrated, and the crude product was chromatographed (silica gel; CHCl3 /MeOH 99:1 to 96:4) to afford a solid (5.2 g, 78% ): 1H NMR (DMSO-d6, 300 MHz) δ2.10 (s, 3H), 5.11 (brs, 2H), 6.95 (dd, J=8.14 Hz, 1H), 7.26 (t, J=2.72 Hz, 1H); MS (CI/NH3) m/z: 127 (M+H)+, 144 (M+NH4)+. |
Here is a chemical reaction formula: Reactants are:m1_m4:FC1=NC=C(C=C1C)I;m2_m5:[Li]C(C)(C)C;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12, Reagents are:m1_m4:CCOCC;m2_m5:CCCCC, and Products are 0:FC1=C(C=C(C=N1)C12CCCN2CCC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Fluoro-5-iodo-3-methylpyridine (200 mg, 0.84 mmol) was dissolved in Et2O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 1.1 mL, 1.80 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (265 mg, 1.26 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with stirring for 2 hours. The cold bath was removed, 2N HCl was added, and the phases were separated. The aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (123 mg, 67%) 1H NMR (CDCl3, 300 MHz) δ1.55-1.71 (m, 2H), 1.78-2.04 (m, 6H), 2.26 (s, 3H), 2.64-2.72 (m, 2H), 3.11-3.18 (m, 2H), 7.70 (m, 1H), 8.09 (m, 1H); MS (CI/NH3) m/z: 221 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:FC1=C(C=C(C=N1)C12CCCN2CCC1)C, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.FC1=C(C=C(C=N1)C12CCCN2CCC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(6-Fluoro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.52 mmol, from step 18d) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound (white needles, 92 mg, 69%): mp 170-171° C.; 1H NMR (D2 O, 300 MHz) δ2.12-2.47 (m, 9H), 2.56-2.66 (m, 2H), 3.32-3.41 (m, 2H), 3.77-3.86 (m, 2H), 7.94 (m, 1H), 8.14 (m, 1H); MS (CI/NH3) m/z: 221 (M+H)+ ; MS (CI/NH3): m/z 221 (M+H+). Anal. Calcd for C13H17FN2.HCl: C, 60.82; H, 7.07; N, 10.91. Found: C, 60.83; H, 6.80; N, 10.63. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=NC=C(C=C1C)[N+](=O)[O-], Reagents are:m3:[Fe];m1_m2:O.CC(=O)O, and Products are 0:NC=1C=C(C(=NC1)Cl)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.) was dissolved in a solution of H2O/AcOH (5:1, 60 mL). Iron powder was added to the reaction mixture while maintaining the temperature below 40° C., and the mixture was stirred for 5 hours. The mixture was filtered through celite and the aqueous filtrate was extracted with EtOAc (4×). The filter cake was washed with EtOAc, and the EtOAc solutions were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford an orange solid (2.3 g, 89%): 1H NMR (CD3OD, 300 MHz) δ2.25 (s, 3H), 7.01 (d, J=2.0 Hz, 1H), 7.58 (d, J=2.0 Hz, 1H); MS (CI/NH3) m/z: 243/245 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3:ClC1=C(C=C(C=N1)C12CCCN2CCC1)C;m4_m2:Cl, Reagents are:m1_m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.ClC1=C(C=C(C=N1)C12CCCN2CCC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (245 mg, 1.03 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound as white plates: mp 179°-180° C.; 1H NMR D2O, 300 MHz) δ2.14-2.48 (m, 9H) 2.56-2.65 (m, 2H), 3.34-3.42 (m, 2H), 3.79-3.87 (m, 2H), 7.89 (d, J=3.0 Hz, 1H), 8.33 (d. J=3.0 Hz, 1H); MS (CI/NH3) m/z: 237/239 (M+H)+ ; MS (CI/NH3): m/z 237 (M+H+). Anal. Calcd for C13H17ClN2.HCl.0.2 HCl: C, 55.67; H, 6.54; N, 9.99. Found: C, 55.90; H, 6.57; N, 9.76. |
Here is a chemical reaction formula: Reactants are:m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m1_m4:IC=1C=CC(=NC1)C;m2_m5:[Li]C(C)(C)C, Reagents are:m1_m4:CCOCC;m2_m5:CCCCC, and Products are 0:CC1=CC=C(C=N1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-Iodo-2-methylpyridine (345 mg, 1.39 mmol) was dissolved in Et2O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 1.8 mL, 3.06 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (435 mg, 2.1 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with stirring for 2 hours. The cold bath was removed, 2N HCl was added, and the phases were separated. The aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 95:5) to afford the title compound as an oil (126 mg, 45%): 1H NMR (CDCl3, 300 MHz) δ1.57-1.71 (m, 2H), 1.77-2.05 (m, 6H), 2.52 (s, 3H), 2.64-2.72 (m, 2H), 3.12-3.19 (m, 2H), 7.05 (d, J=8.1 Hz, 1H), 7.71 (dd, J=8.1, 2.6 Hz, 1H), 8.56 (d, J=2.6 Hz, 1H); MS (CI/NH3) m/z: 203 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:CC1=CC=C(C=N1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.Cl.CC1=CC=C(C=N1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(6-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.57 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound as a free flowing white powder: mp 205°-208° C.; 1H NMR D2O, 300 MHz) δ2.14-2.49 (m, 6H), 2.57-2.66 (m, 5H), 3.34-3.42 (m, 2H), 3.78-3.87 (m, 2H), 7.56 (d, J=8.1 Hz, 1H), 8.05 (dd, J=8.1, 2.7 Hz, 1H), 8.61 (d, J=2.7 Hz, 1H); MS (CI/NH3) m/z: 203 (M+H)+ ; MS (CI/NH3): m/z 203 (M+H+); Anal. Calcd for C13H18N2.2 HCl.0.8 H2O: C, 53.91; H, 7.52; N, 9.67. Found: C, 53.80; H, 7.46; N, 9.68. |
Here is a chemical reaction formula: Reactants are:m3:[H-].[H-].[H-].[H-].[Li+].[Al+3];m4:[H-].[H-].[H-].[H-].[Li+].[Al+3];m1_m2_m5:ClC1=C(C=C(C=N1)C12CCCN2CCC1)C;m1_m2_m5:[H-].[H-].[H-].[H-].[Li+].[Al+3], Reagents are:m1_m2_m5:C1CCOC1, and Products are 0:CC=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (274 mg, 1.16 mmol, from Example 19c) and LAH (1.0M in THF, 1.2 mL, 1.16 mmol) were added to THF (4.5 mL), and the mixture was stirred at room temperature for 4 hours. An additional amount of LAH (1.0M in THF, 1.2 mL, 1.16 mmol) was added, and the reaction was stirred overnight. A further amount of LAH (2 equivalents) was added, and the reaction was stirred at room temperature for 24 hours and at 80° C. for 5 hours. The reaction was quenched with 10% K2CO3 solution, and the resulting slurry was filtered. The filtrate was diluted with EtOAc and 15% NaOH, and the phases were separated. The aqueous phase was extracted with methylene chloride, and all the organic solutions were combined, dried and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford the title compound as an oil (116 mg, 49%): 1H NMR (CDCl3, 300 MHz) δ1.57-1.71 (m, 2H), 1.77-2.06 (m, 6H), 2.32 (s, 3H), 2.66-2.74 (m, 2H), 3.12-3.19 (m, 2H), 7.63 (s, 1H), 8.24 (s, 1H), 8.50 (s, 1H); MS (CI/NH3) m/z: 203 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:CC=1C=C(C=NC1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.CC=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (109 mg, 0.54 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (112 mg, 87%); mp 153°-154° C.; 1H NMR D2O, 300 MHz) δ2.12-2.49 (m, 9H), 2.57-2.66 (m, 2H), 3.34-3.43 (m, 2H), 3.79-3.87 (m, 2H), 7.90 (s, 1H), 8.46 (s, 1H), 8.52 (s, 1H); MS (CI/NH3) m/z: 203 (M+H)+ ; MS (CI/NH3): m/z 203 (M+H+), 220 (M+NH4+). Anal. Calcd for C13H18N2.1.4 HCl: C, 61.63; H, 7.72; N, 11.06. Found: C, 61.82; H, 7.89; N, 11.00. |