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Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC=1C=C(C=CC1OC)C1(CC=CC=C1)C=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)C2(CC=CC=C2)C=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2 benzisoxazole (2.01 g; 9.13 mmol), K2CO3 (2.0 g), and 1-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenylmethanone (3.93 g; 11.3 mmol) and acetonitrile (50 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was evaporated and the residue was partitioned between water (150 ml) and dichloromethane (400 ml). The dichloromethane solution was washed with water and brine (100 ml), dried over MgSO4, then concentrated to an oil. The purification was done by flash chromatography over a silica gel column (SiO2, 40 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 850 ml). The material thus obtained as a colorless oil solidified on standing. Recrystallization from ethanol (150 ml) gave 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]phenylmethanone as white crystals, 3.07 g (63%), m.p.=140°-141° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC=1C=C(C=CC1)C(C)=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2)C(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.53 g, 20.5 mmol), K2CO3 (4.5 g), 1-[3-(3-chloropropoxy)phenyl]ethanone (6.4 g, 29 mmol) in acetonitrile (60 ml) was heated at reflux for 5 hours. At the end of the reaction, the solvent was removed and the residue was extracted into dichloromethane (300 ml). The inorganic insolubles were filtered off. The dichloromethane solution was concentrated to a small volume (10 ml) and purified on a flash chromatographic column (SiO2, 75 g, eluted with dichloromethane, 900 ml; and 2% methanol in dichloromethane, 800 ml). The fractions containing the pure product were combined and concentrated to an oil (2.87 g, 35%). The oil was dissolved into ethanol and treated with a solution of fumaric acid (841 mg). Recrystallization (twice) from ethanol afforded 2.53 g of 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3yl)-1-piperidinyl]propoxy]phenyl]ethanone fumarate as white crystals, m.p.=172°-174° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m5_m6:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5_m6:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5_m6:BrCCCOC=1C=C(C=CC1OC)NC(C)=O, amount is: 0.0 ;m4_m8:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m7:C(C)O, amount is: 0.0 MOLE;m1_m2_m3_m5_m6:CN(C=O)C, amount is: 0.0 ;m1_m2_m3_m5_m6:C(C)#N, amount is: 0.0 ;m4_m8:C(C)O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)NC(C)=O)C=C1.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)NC(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.94 g, 15.4 mmol), K2CO3 (3.67 g, 26.6 mmole), N-[3-(3-bromopropoxy)-4-methoxyphenyl]acetamide (5.56 g, 18.6 mmol) in dimethylformamide (75 ml) and acetonitrile (100 ml) was heated at 100° C. for 3 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (500 ml). The organic solution was washed with water (500 ml) and brine (400 ml), dried, then concentrated to a crude oil. The purification was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3 OH:dichloromethane, 500 ml). The material thus obtained weighed 2.33 g (34.3%) as an oil. This material was dissolved in ethanol and treated with a solution of fumaric acid (661 mg) in ethanol. The N-[3-[3-[4-(6-fluoro-1,2 benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate was obtained as off-white crystals weighing 2.17 g, m.p.=205°-206° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3:FC1=CC=C2C(=NNC2=C1)C1CCNCC1, amount is: 0.0 ;m1_m2_m3:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3:ClCCCOC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m4:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CCCOC1=C(C=C(C=C1)C(C)=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1H-indazole (3.5 g, 16 mmol), K2CO3 (2.2 g), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (3.8 g, 16 mmol) acetonitrile (90 ml) was refluxed for 16 hours. The reaction was poured into water and the resulting white solid, which precipitated from solution, was collected to afford 5.5 g of the desired product. The compound was recrystallized from dimethylformamide (twice) to afford 3.0 g (44%) of 1-[4-[3-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]propoxy]-methoxyphenyl]ethanone as a white solid, m.p.=202°-204° C. |
Here is a chemical reaction formula: Reactants are m4_m8:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ;m1_m2_m3_m5_m6:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5_m6:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5_m6:BrCCCOC1=C(C=C(C=C1)C(C)=O)C, amount is: 0.0 ,this reaction does not need reagents,Solvents are m7:C(C)O, amount is: 0.0 MOLE;m4_m8:C(C)O, amount is: 0.0 MOLE;m1_m2_m3_m5_m6:CN(C=O)C, amount is: 0.0 ;m1_m2_m3_m5_m6:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)C)C=C1.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)C)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.0 g; 11.7 mmol), K2CO3 (3.0 g), and 1-[4-(3-bromopropoxy)-3-methylphenyl]ethanone (3.19 g) in dimethylformamide (20 ml) and acetonitrile (50 ml) was heated at 95° C. for 4 hours. At the end of the reaction, the solvent was concentrated down to about 30 ml, then partitioned between water (200 ml) and dichloromethane (300 ml). The dichloromethane solution was separated and washed with water and brine, then dried over MgSO4. The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml). The material thus obtained was a light yellow oil, weight: 2.07 g (43%). This oil was dissolved in ethanol and treated with a solution of fumaric acid (585 mg) in ethanol. The 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methylphenyl]ethanone hemifumarate crystals formed on cooling at 0° C. This was collected and weighed 1.5 g, m.p.=185°-187° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C#N)C=C1)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C#N)C=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), K2CO3 (2.8 g), 4-(3-bromopropoxy)-3-methoxybenzonitrile (4.0 g, 14.8 mmol) in acetonitrile (70 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was removed on a rotary evaporator. The organic material was extracted into dichloromethane (250 ml) and the inorganics were filtered off. The dichloromethane solution was concentrated to a crude oil. The purification was done by flash chromatography over a silica gel column (SiO2, 55 g; eluted with dichloromethane, 600 ml; 1% methanol in dichloromethane, 600 ml). The material thus obtained was crystallized from a small amount of dichloromethane. Recrystallization from ethanol (25 ml) provided 3.8 g (68%) of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzonitrile as white crystals, m.p.=107°-108° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1Br)C(C)=O)Br, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrC=1C=C(C=C(C1OCCCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F)Br)C(C)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.0 g, 9.0 mmol), K2CO3 (1.3 g), and 1-[4-(3-bromopropoxy)-3,5-dibromophenyl]ethanone (2.65 g, 9.0 mmol) and acetonitrile (50 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was evaporated and the residue was extracted into dichloromethane (150 ml). The insolubles were filtered off. The dichloromethane solution was concentrated down to an oil. The purification was done by flash chromatography on a silica gel column (SiO2, 47 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 600 ml). The material thus purified as a colorless oil, solidified on standing. Recrystallization from ethanol gave 1-[3,5-dibromo-4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone as white crystals (2.93 g, 57%), m.p.=102°-103° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=CC=CC=C1, amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=CC=CC=C2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.0 g, 18.2 mmol), K2CO3 (3.0 g, 21.8 mmol), KI (100 mg), 3-chloropropoxybenzene (3.4 g, 20.0 mmol), and acetonitrile was stirred at reflux under nitrogen for 30 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried with MgSO4 and concentrated to afford 6.2 g of a damp, beige solid. The compound was recrystallized twice from ethanol to yield (47%) of 6-fluoro-3-[1-(3-phenoxypropyl)-4-piperidinyl]-1,2-benzisoxazole as a light beige solid, m.p.=78°-80° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C(F)(F)F)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C(F)(F)F)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (1.5 g, 6.7 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone (2.0 g, 6.7 mmol), K2CO3 (0.88 g), KI (0.1 g) and acetonitrile (50 ml) was stirred and refluxed for 16 hours. After cooling, the reaction was poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed (H2O), dried (MgSO4), and the solvent was concentrated to an oil, which upon evacuation at high vacuum afforded 3.2 g of a waxy solid. The solid was chromatographed on a Waters preparative LC (silica columns, eluting with 3% methanol-dichloromethane). Concentration of the appropriate fractions gave 1.8 g (56%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoro-ethanone solid, m.p.=94°-96° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:CC(=O)C1=CC(=C(C(=C1)Br)O)Br, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrCCCOC1=C(C=C(C=C1Br)C(C)=O)Br, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 3,5-dibromo-4-hydroxyacetophenone (3.0 g, 10.1 mmol), K2CO3 (2.8 g, 20.3 mmol), 1,3-dibromo-propane (4.0 g, 19.8 mmol) in acetonitrile (100 ml) was heated at reflux for 5 hours. The solvent was removed. The crude product was extracted into dichloromethane (150 ml) and the insoluble inorganics were filtered off. The solution was concentrated to dryness again. Purification was carried out by flash chromatography on silica gel (45 g, SiO2 ; eluted with 1:1 hexane:dichloromethane). The material thus obtained (2.8 g) was recrystallized twice from isopropyl ether to give analytically pure 1-[4-(3-bromopropoxy)-3,5-dibromophenyl]ethanone, m.p.=87°-88° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1)C1(CC=CC=C1)C=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C2(CC=CC=C2)C=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10 mmol), K2CO3 (2.3 g) and 1-[4-(3-bromopropoxy)-3-methoxyphenyl]phenylmethanone (3.47 g, 10 mmol) in acetonitrile (100 ml) was heated at reflux for 3 hours. At the end of reaction, the acetonitrile was concentrated and the mixture was extracted into dichloromethane (200 ml). The insolubles were filtered off and the solvent was evaporated to an oil. Purification was carried out by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 600 ml; 1% methanol:dichloromethane, 600 ml; 2% methanol: 98% dichloromethane, 600 ml). The fractions containing the pure product were combined and concentrated to give 4.24 g (87%) of an off-white solid. Recrystallization from ethanol (75 ml) gave 3.9 g of 1-[4-[3-[4-(6-fluoro-1,2-benziosoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]phenylmethanone as off-white crystals, m.p.=128°-130° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1)CC(CCC)=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)CC(CCC)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10 mmol), K2CO3 (3 g), 1-[4-(3-bromopropoxy)-3-methoxyphenyl]pentanone (3.7 g, 11.3 mmol) in acetonitrile (140 ml) was heated at reflux for 4 hours. At the end of the reaction, the mixture was cooled and filtered. The filtrate was concentrated to an oil. Purification was performed by flash chromatography over a silica gel column (SiO2, 55 g; eluted with 1% methanol in dichloromethane, 600 ml; 3% methanol: 97% dichloromethane, 400 ml). The fractions containing pure product were pooled and concentrated to a solid (4.3 g, 91%). Recrystallization from ethanol (10 ml) gave a powdery solid of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]pentanone (3.22 g), m.p.=79°-80° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1)CC(C)=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)CC(C)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.8 g, 15.2 mmol), K2CO3 (3 g), 1-[4-(3-bromopropoxy)-3-methoxyphenyl]propanone (4.6 g, 18.2 mmol) in acetonitrile (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the mixture was filtered and the solvent was concentrated and the residue was extracted into dichloromethane (300 ml). The dichloromethane was filtered and concentrated again. The crude material (6.4 g) was purified by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 700 ml; 1% methanol in dichloromethane, 1.4 l). The material thus purified (weight: 2.87 g, 51%) was recrystallized from ethanol (25 ml) to give 2.13 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]propanone as beige colored crystals, m.p.=118°-119° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C(=O)N)C=C1)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C(=O)N)C=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10.0 mmol), K2CO3 (2.0 g) and 4-(3-bromopropoxy)-3-methoxybenzamide (2.32 g, 8.0 mmol) in acetonitrile (80 ml) was heated at reflux for 5 hours. At the end of the reaction the solvent was evaporated. The residue was extracted into dichloromethane. The inorganic insolubles were filtered off. The dichloromethane was concentrated again. The crude residue was purified by flash chromatography over a silica gel column (55 g, SiO2 ; eluted with 1% methanol in dichloromethane, 1 l; 2% methanol in dichloromethane, 1 l). The material thus obtained weighed 2.93 g (84%) as white crystals. Recrystallization from hot ethanol (60 ml) gave 2.2 g of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzamide as white crystals, m.p.=163°-164° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)NC, amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:CO.C(Cl)Cl, amount is: 0.0 MOLE;m6:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)NC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.3 g, 10.3 mmol), K2CO3 (1.4 g, 10.3 mmol), 1-[4-(3-chloropropoxy)-3-(methylamino)phenyl]ethanone (2.5 g, 10.3 mmol), KI (0.10 g), and acetonitrile (100 ml) was stirred at reflux under nitrogen for 23 hours. The reaction was cooled to ambient temperature, poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed twice with water, dried with MgSO4 and was concentrated to yield 4.8 g of a damp, brown solid. The compound was isolated by preparative HPLC (Waters Associates prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent). Concentration of appropriate fractions afforded 2.4 g. Recrystallization from ethanol gave 2.1 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-(methylamino)phenyl]ethanone as a beige solid, m.p.=151°-153° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:OC1=C(C=C(C=C1)C(C)=O)SC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrCCCOC1=C(C=C(C=C1)C(C)=O)SC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 1-[4-hydroxy-3-(methylmercapto)phenyl]-ethanone (5.4 g; 30 mmol), K2CO3 (4.2 g), 1,3-dibromopropane (8 g, 39 mmol) in acetonitrile (150 ml) was heated at reflux for 3 hours and stirred at room temperature overnight. Acetonitrile was removed at reduced pressure and the residue was extracted into dichloromethane (250 ml). Insolubles were filtered off. The dichloromethane solution was concentrated. The crude product was purified on a silica gel column (SiO2, 100 g; eluted with 3:2 hexane:dichloromethane, 1.6 l). The compound crystallized upon concentration, and the product (3.5 g, 39%) was recrystallized from ethanol (40 ml) to yield 1-[4-(3-bromopropoxy)-3-(methylmercapto)phenyl]ethanone as white needles, 2.0 g: m.p.=120°-122° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:OC1=C(C=C(C=C1)C1(CC=CC=C1)C=O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrCCCOC1=C(C=C(C=C1)C1(CC=CC=C1)C=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 1-(4-hydroxy-3-methoxyphenyl)phenyl-methanone (14 g, 61.4 mmol), K2CO3 (13 g, 92.1 mmol), and 1,3-dibromopropane (28 g, 86 mmol) in acetonitrile (400 ml) was heated at reflux for 4 hours. The reaction was followed by thin layer chromatography. At the end of the reaction, the inorganics were filtered off and the solvent was removed on a rotary evaporator. The residue was purified on a flash chromatographic column (SiO2, 140 g, eluted with 4:1 hexane:dichloromethane, 1.2 l) to give a partially solidified material: 15.44 g (72%). Recrystallization twice from ethanol gave 2.84 g of 1-[4-(3-bromopropoxy)-3-methoxyphenyl]phenylmethanone as white crystals, m.p.=88°-89° C. |
Here is a chemical reaction formula: Reactants are m1_m3:ClCCCOC1=C(C=C(C(=O)O)C=C1)OC, amount is: 0.0 ;m2:S(=O)(Cl)Cl, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3:ClCCl, amount is: 0.0 ;m4:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCOC1=C(C=C(C(=O)Cl)C=C1)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a mixture of 4-(3-chloropropoxy)-3-methoxybenzoic acid (2.4 g, 10 mmol) in dichloromethane (5 ml) was added thionyl chloride (0.9 ml, 12 mmol) dissolved in dichloromethane (5 ml). The reaction was stirred and refluxed for 1 hour, and then the dichloromethane was removed in vacuo to leave a dark oil. The oil was triturated with hexane and the solid that formed while scratching with a glass rod was collected to afford 1.6 g of 4-(3-chloropropoxy)-3-methoxybenzoyl chloride, m.p.=60°-63° C. |
Here is a chemical reaction formula: Reactants are m3:[BH4-].[Na+], amount is: 0.0 ;m2_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)O, amount is: 0.0 ;m1:[BH4-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m2_m4:C(C)O.O1CCCC1, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCOC1=C(C=C(C=C1)C(O)C)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a flask charged with sodium borohydride (1.5 g, 39.4 mmol) under nitrogen and chilled to 10° C. was added, slowly, a solution of 1-[4-(3-chloropropoxy)-3-hydroxyphenyl]ethanone (6.0 g, 26.2 mmol) dissolved in ethanol-tetrahydrofuran (120 ml, 2:1). After total addition, the ice bath was removed and the reaction was stirred at ambient temperature for 3 hours. An additional amount of sodium borohydride (0.2 g, 5.3 mmol) was carefully added. After stirring at ambient temperature for one hour, the solvent was removed in vacuo. The resultant solid residue was diluted with water (100 ml) and left overnight. The product was isolated by vacuum filtration yielding 3.8 g. Two consecutive recrystallizations from toluene provided 3.3 g (55%) of 4-(3-chloropropoxy)-3-hydroxy-α-methylbenzene methanol as a light brown solid, m.p.=107°-109° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(O)C)O, amount is: 0.0 ;m1_m2_m3_m4:C(=O)(O)[O-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:CC#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(O)C)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.3 g, 19.5 mmol), 4-(3-chloropropoxy)-3-hydroxy-α-methylbenzenemethanol (4.5 g, 19.5 mmol), KI (200 mg), NaHCO3 (1.8 g, 21.5 mmol) and CH3CN (125 ml) was stirred at reflux under nitrogen for 24 hours. The cooled reaction was filtered and the filter cake was washed with CH3CN. The filtrate was concentrated to afford an oily residue, which was partitioned between water and ethyl acetate. The ethyl acetate extract was washed with water, dried with MgSO4, and concentrated to yield 8.6 g of a dark oil. The oil was purified by preparative HPLC (Waters Associates prep LC/system 500) to yield 5.0 g. The compound was recrystallized twice from ethanol to provide 3.9 g (49%) of 4-[3-4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-hydroxy-α-methyl-benzene methanol as a light beige solid, m.p.=142°-144° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:C(C)(=O)NC=1C=C(C=CC1O)C(C)=O, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:CC(=O)C, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(C)(=O)NC=1C=C(C=CC1OCCCCl)C(C)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 1-[3-acetylamino-4-hydroxyphenyl]ethanone (7.7 g, 40 mmol), K2CO3 (5.7 g), 3-chloro-1-bromopropane (8.9 g, 56 mmol) and acetone (100 ml) was refluxed for 16 hours. The reaction was allowed to cool to ambient temperature and filtered. Concentration of the filtrate yielded 8.5 g of a white solid. The solid was recrystallized from toluene and then from ethanol to afford 6.5 g of an off-white solid. A 3.3 g sample of this material was flash chromatographed on silica gel with ethyl acetate as eluent. Concentration of the appropriate fractions afforded 2.8 g of a solid. The solid was recrystallized from toluene and then from ethanol-water to yield 2.2 g (51%) of a solid, m.p.=124°-126° C. |
Here is a chemical reaction formula: Reactants are m1_m2:CC(=O)C1=CC(OC)=C(O)C=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2:C(C)O, amount is: 0.0 ,Catalysts are m4:Cl, amount is: 0.0 MOLE;m3:[Pd], amount is: 0.0 .Products are 0:C(C)C1=CC(=C(C=C1)O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Acetovanillone (Aldrich, 11.0 g, 66 mmol) was dissolved in absolute ethanol (200 ml) and added to 1.5 g of 5% palladium on carbon. A few drops of concentrated hydrochloric acid were added and the mixture hydrogenated on a shaker at 42 psi. The reaction mixture was filtered through Celite, and the filtrate was concentrated to afford 10.3 g of a golden liquid. This was diluted with water, extracted with diethyl ether and the organic phase was washed with water and sodium bicarbonate. The solvent was dried (MgSO4), and concentrated to afford 9.3 g of a slightly yellow liquid. |
Here is a chemical reaction formula: Reactants are m3:BrCCCBr, amount is: 0.0 ;m1_m4_m2:C(C)(=O)NC=1C=C(C=CC1)O, amount is: 0.0 ;m1_m4_m2:C([O-])([O-])=O.[K+].[K+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(C)(=O)NC=1C=C(OCCCBr)C=CC1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To 3-acetamidophenol (15.1 g) in dichloromethane (500 ml, dry) was added potassium carbonate (20 g) and then 1,3-dibromopropane (30 g). The resulting mixture was heated at reflux for 6 hours and then overnight at room temperature. After an additional 24 hours, the reaction was complete. Solids were filtered from the reaction mixture, and the solution was concentrated to an oil, which was purified to yield 3-(3-acetamidophenoxy)propyl bromide, 13.2 g. |
Here is a chemical reaction formula: Reactants are m1:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2)NC(C)=O)C=C1, amount is: 0.0 ;m2:[OH-].[Na+], amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m3:Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(N)C=CC2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of N-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidiny]propoxy]phenyl]acetamide (9.2 g, 22 mmol), prepared as described in the previous example, in 15% hydrochloric acid (110 ml) was heated at 100° C. for 2.5 hours until a homogeneous solution resulted. The reaction was cooled to 0° C. in an ice bath and basified with 50% NaOH. The product was extracted with ethyl acetate (3×200 ml). The ethyl acetate solution was washed with water, brine, then dried over Na2SO4. The solvent was removed. The crude product was purified on a flash chromatography column. The product thus obtained was a solid: 6.6 g (80%). Recrystallization from hot ethanol (50 ml) gave 3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-aniline as off-white crystals: 3.46 g, m.p.=115°-117° C. |
Here is a chemical reaction formula: Reactants are m3:BrCCCBr, amount is: 0.0 ;m1_m4_m2:CN(C(C1=CC(=C(C=C1)O)OC)=O)C, amount is: 0.0 ;m1_m4_m2:C([O-])([O-])=O.[K+].[K+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:CN(C(C1=CC(=C(C=C1)OCCCBr)OC)=O)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To N,N-dimethyl-4-hydroxy-3-methoxybenzamide (5.64 g, 28.7 mmol) in acetonitrile (450 ml) was added potassium carbonate (7.9 g) followed by 1,3-dibromopropane (11.6 g). The resulting reaction mixture was refluxed for 3 hours and stirred at room temperature for 12 hours. The mixture was filtered and concentrated to an oil. Following purification by column chromatography, N,N-dimethyl-4-bromopropoxy-3-methoxybenzamide as a colorless oil (7.6 g) was obtained. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:CN(C(C1=CC(=C(C=C1)OCCCBr)OC)=O)C, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:CN(C(C1=CC(=C(C=C1)OCCCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F)OC)=O)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.9 g, 17.7 mmol), N,N-dimethyl-4-bromopropoxy-3-methoxybenzamide (5.54 g, 17.5 mmol) and K2CO3 (3 g) in acetonitrile (250 ml) was heated at reflux for one hour. At the end of the reaction, the insolubles were filtered and washed with dichloromethane. The solvent was removed on a rotary evaporator. The residue was purified by flash chromatography over a silica gel column. The product thus obtained as an oil weighed 7 g. Crystallization from hot ethanol (45 ml) afforded analytically pure N,N-dimethyl-4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzamide, 3.95 g, 50%, as light yellow crystals, m.p.=126°-127° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)OC)C=C1, amount is: 0.0 ;m1_m2_m3:NN, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3:C(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=NN)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (4.3 g, 10 mmol), prepared as in Example 3 above, hydrazine (0.8 g, 2.5 mmol), and ethanol (40 ml) was refluxed for 16 hours. The cooled solution was concentrated to yield an oily residue. The residue was triturated with water and the resultant solid was collected to afford 4.2 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone hydrazone as a yellow solid. The compound was recrystallized from isopropanol and then from toluene to afford 1.7 g (39%), m.p.=106°-108° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:CC(=O)C1=CC(=C(C=C1)O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClC\C=C/CCl, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClC\C=C/COC1=C(C=C(C=C1)C(C)=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 4-hydroxy-3-methoxyacetophenone (16.6 g, 10 mmole), K2CO3 (14 g, 100 mmol) and cis-1,4-dichloro-2-butene (Aldrich, 15 g, 120 mmol) in acetonitrile (250 ml) was heated at reflux for 2.5 hours. The mixture was filtered and concentrated to an oil. Purification was by flash chromatography. The fractions containing the purest product were combined and concentrated to give white crystals, 7.7 g, 30%. This was recrystallized from ether to give analytical pure (Z)-1-[4-[(4-chloro-2-butenyl)oxy]-3-methoxyphenyl]ethanone (2.72 g), m.p.=64°-66° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:FC1=CC2=C(C(=NO2)C2CCN(CC2)C/C=C/COC=2C=C(C=CC2OCC2=CC=CC=C2)C(C)=O)C=C1, amount is: 0.0 ;m1_m3_m2:Cl, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3_m2:C(C)(=O)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:Cl.FC1=CC2=C(C(=NO2)C2CCN(CC2)C/C=C/COC=2C=C(C=CC2O)C(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The mixture of (E)-1-[3-[[4-(4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-butenyl]oxy]-4-benzyloxyphenyl]ethanone (5.5 g, 10.7 mmol), acetic acid (50 ml), and hydrochloric acid (6 ml) was heated at 75° C. for 2 hours. At the end of reaction, the solvent was reduced to about 20 ml on a rotary evaporator. The solution was poured into ice water (350 ml) and extracted with dichloromethane (3×250 ml). The dichloromethane solution was washed with brine and dried over Na2SO4. A solid formed on concentration of the solvent. This was collected by filtration (3.4 g). Recrystallization from hot methanol (40 ml) gave 1.82 g of (E)-1-[3-[[4-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-butenyl]oxy]-4-hydroxyphenyl]ethanone hydrochloride as white crystals, 37.5%, m.p.=208°-210° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:CS(=O)(=O)OCC1COC2=C(O1)C=CC=C2, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CC2COC3=C(O2)C=CC=C3)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), K2CO3 (2.45 g, 17.7 mmol), 2-methanesulfonyloxymethyl-1,4-benzodioxan (3.35 g, 13.7 mmole) in acetonitrile (100 ml) was heated at reflux for 12 hours. At the end of the reaction, the insolubles were filtered and rinsed with dichloromethane. The organic solution was concentrated. The crude oil was purified by flash chromatography on a silica gel column. The fractions containing the pure product were pooled and concentrated to a light yellow oil (3.94 g, 74%). Crystallization from ethanol and petroleum ether gave 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl-1,4-benzodioxan as off-white crystals, 2.22 g, m.p.=86°-87° C. |
Here is a chemical reaction formula: Reactants are m3:S(=O)(=O)(C)Cl, amount is: 0.0 ;m1_m4_m2:OCCC1COC2=C(O1)C=CC=C2, amount is: 0.0 ;m1_m4_m2:C(C)N(CC)CC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:S(=O)(=O)(C)OCCC1COC2=C(O1)C=CC=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To the compound 2-hydroxyethyl-1,4-benzodioxan (11.96 g) in dichloromethane (450 ml) was added triethylamine (0.12 mol, 10 ml). Mesylchloride (9.2 g) was then added dropwise and the reaction mixture was stirred for one hour at room temperature. After completion of the reaction, the solution was washed with water, brine, and concentrated to an oil, which was purified by chromatography on silica gel to yield 2-mesyloxyethyl-1,4-benzodioxan, 17.08 g. |
Here is a chemical reaction formula: Reactants are m3_m4:BrCCCCl, amount is: 0.0 ;m1_m2_m5:OC=1C=C2CCCC(C2=CC1OC)=O, amount is: 0.0 ;m1_m2_m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m3_m4:CC(=O)C, amount is: 0.0 ;m1_m2_m5:CC(=O)C, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCOC=1C=C2CCCC(C2=CC1OC)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-hydroxy-7-methoxy-1-tetralone (J. Org. Chem., 1985, 50, 4937) (1.5 g, 7.8 mmol), K2CO3 (1.7 g, 12.3 mmol), and acetone (30 ml) was stirred at reflux under nitrogen for 45 minutes. The reaction was cooled to ambient temperature and a solution of 1-bromo-3-chloropropane (1.9 g, 12.1 mmol) dissolved in 8 ml acetone was dripped into the mixture. After total addition, the reaction was heated to reflux and stirred under nitrogen for 21 hours. The reaction was cooled to ambient temperature and filtered. The filter cake was washed well with acetone and the filtrate was concentrated to yield 2.0 g 6-(3-chloropropoxy)-7-methoxy-1-tetralone as an amber oil. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCN1C(C=2C(C1=O)=CC=CC2)=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCN2C(C=3C(C2=O)=CC=CC3)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (6.44 g, 29.1 mmole), K2CO3 (6.4 g, 46 mmol), N-(3-bromopropyl)phthalimide (8.4 g, 31 mmol) in acetonitrile (150 ml) was heated at reflux for 3.5 hours. The insolubles were filtered. The solvent was removed at reduced pressure and the residue was purified by silica gel column chromatography to give N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propyl]phthalimide as a white solid. Recrystallization from ethanol yielded 9.8 g (83%) of off-white crystals, m.p.=129°-130° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m6:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCN2C(C=3C(C2=O)=CC=CC3)=O)C=C1, amount is: 0.0 ;m1_m2_m6:O.NN, amount is: 0.0 ;m5_m7:Cl, amount is: 0.0 MOLE;m3:O, amount is: 0.0 ;m4:Cl, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m1_m2_m6:CO, amount is: 0.0 ;m5_m7:C(C)O, amount is: 0.0 MOLE;m8:CO, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:Cl.Cl.NCCCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propyl]phthalimide (8.5 g, 21 mmol), hydrazine monohydrate (1.5 g, 30 mmol) in methanol (60 ml) was heated at reflux for 2 hours. At the end of the reaction, methanol was removed to leave a crude solid. To this was added water (60 ml), then the mixture was acidified with HCl to pH 1. The insolubles were filtered with the aid of a pad of Celite. The aqueous solution was basified with 50% NaOH, (pH 13), then extracted with dichloromethane. The combined dichloromethane solution was washed with brine, then dried to a colorless oil (4.5 g). The analytical sample (1.5 g) was prepared by treating the oil with HCl in ethanol at 0° C. The 1-(3-aminopropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine dihydrochloride was obtained as white crystals, 2.03 g, m.p.=231°-234° C. |
Here is a chemical reaction formula: Reactants are m4_m7:Cl, amount is: 0.0 MOLE;m1_m2_m5:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCCN2C(C=3C(C2=O)=CC=CC3)=O)C=C1, amount is: 0.0 ;m1_m2_m5:O.NN, amount is: 0.0 ;m3:Cl, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m4_m7:C(C)O, amount is: 0.0 MOLE;m8:CO, amount is: 0.0 MOLE;m1_m2_m5:CO, amount is: 0.0 ;m6:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:Cl.Cl.NCCCCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of N-[4-[4-(6-fluoro-1,2-benzisoxazol-3-yl) piperidinyl]butyl]phthalimide (6.9 g, 16.4 mmol) and hydrazine monohydrate (1.64 g, 32.8 mmol) in methanol (70 ml) was heated at reflux for 3 hours. At the end of the reaction, methanol was removed to leave a crude solid. This was dissolved in water and acidified with HCl to pH 2. The insolubles were filtered. The aqueous solution was basified with 50% NaOH, and then extracted with dichloromethane. The dichloromethane solution was washed with water and brine, and then dried over MgSO4. The solvent was removed to a colorless oil: 4.48 g. This oil was treated with 2.5 equivalents of HCl in ethanol. The solid was collected. Recrystallization from ethanol (65 ml) and methanol (20 ml) gave 2.0 g of 1-(4-aminobutyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine dihydrochloride as white crystals, m.p.=234°-237° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m6:CC(=O)C1=CCC(=S)C(=C1)OC, amount is: 0.0 ;m1_m2_m6:C([O-])([O-])=O.[K+].[K+], amount is: 0.0 ;m3_m5:BrCCCCl, amount is: 0.0 ;m4:C1CCCCC1, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m1_m2_m6:CC(=O)C, amount is: 0.0 ;m3_m5:CC(=O)C, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCSC1=C(C=C(C=C1)C(C)=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 1-(4-thio-3-methoxyphenyl)ethanone (10.0 g, 54.9 mmol), potassium carbonate (9.0 g, 65.1 mmol), and acetone (100 ml) was stirred at reflux under nitrogen for 30 minutes. The reaction was cooled to ambient temperature and a solution of 1-bromo-3-chloropropane (6.5 ml, 9.5 g, 60.4 mmol) dissolved in acetone (25 ml) was dripped into the reaction. After complete addition, the reaction was heated to reflux and stirred under nitrogen for 17 hours. After the reaction was carried to substantial completion, the reaction mixture was filtered and the resulting filter cake was washed with acetone. The filtrate was concentrated to provide an amber oil. A small sample was solidified by trituration with hot cyclohexane to provide 1-[4-[(3-chloropropyl)thio]-3-methoxyphenyl]ethanone as a yellow solid, 11.7 g, m.p.=53°-55° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCSC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:CC#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCSC2=C(C=C(C=C2)C(C)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), 1-[4-[(3-chloropropyl)-thio]-3-methoxyphenyl]ethanone (3.5 g, 13.6 mmol), K2CO3 (2.3 g, 16.6 mmol), KI (200 mg) and CH3CN (100 ml) was stirred at reflux under nitrogen for 7.5 hours and then was left at ambient temperature for 65 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed twice with water, once with brine and dried over MgSO4. The solvent was removed in vacuo to afford 6.8 g of a light brown oil. The sample was purified by flash chromatography. Concentration of appropriate fractions yielded 3.0 g. Recrystallization from ethanol provided 2.4 g (41%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propyl]thio]-3-menthoxyphenyl]ethanone as a beige solid, m.p.=93°-95° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m5:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5:BrCCCCC1=C(C=CC=C1)OC, amount is: 0.0 ;m4_m6:C(\C=C/C(=O)O)(=O)O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m5:C(C)#N, amount is: 0.0 ;m4_m6:C(C)O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:C(\C=C/C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)C(CCC)C2=C(C=CC=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.36 g, 10.7 mmole), K2CO3 (2 g, 14.5 mmol) and 2-(4-bromobutyl)anisole (2.4 g, 10 mmol) in acetonitrile (100 ml) was heated at reflux for 2.5 hours. At the end of reaction, the solvent was removed. The residue was extracted into dichloromethane (200 ml) and filtered. The dichloromethane solution was concentrated. The crude oil obtained was purified on a flash chromatography column. The material thus purified was a light yellow oil (2.73 g, 53%). This oil was dissolved in ethanol and treated with maleic acid (607 mg, 1.0 eq) in ethanol. The 4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-(2'-methoxyphenyl)butylpiperidine maleate crystals formed on concentration and subsequent cooling to 0° C. These were collected and dried to yield 2.05 g, m.p.=132°-133° C. |
Here is a chemical reaction formula: Reactants are m1_m4_m2_m3:BrC1=CC=C(C=C1)C(C)=O, amount is: 0.0 ;m1_m4_m2_m3:C(CCS)S, amount is: 0.0 ;m1_m4_m2_m3:B(F)(F)F.CCOCC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:ClCCl, amount is: 0.0 ;m1_m4_m2_m3:ClC(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrC1=CC=C(C=C1)C(C)C1SCCCS1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To the compound p-bromoacetophenone (36.85 g, 185 mmol) in trichloromethane (300 ml) was added 1,3-propanedithiol (25 g, 230 mmol) and boron trifluoride etherate (3 ml). The resulting mixture was stirred at room temperature for 48 hours. The mixture was diluted with dichloromethane (500 ml), washed twice with 10% sodium hydroxide (200 ml), water, and brine, and then dried (Na2SO4). The product was concentrated to an oil. A portion was stirred with ether (100 ml) and a crystalline product was formed. The crystalline product was recovered by filtration and purified by recrystallization to yield 4-bromo-1-(1,3-dithian-2-yl)ethylbenzene. |
Here is a chemical reaction formula: Reactants are m1_m4_m5_m2_m3:FC1=C(C=CC(=C1)F)C(=O)C1CN(CC1)CC1=CC=CC=C1, amount is: 0.0 ;m1_m4_m5_m2_m3:NO.Cl, amount is: 0.0 ;m1_m4_m5_m2_m3:C(C)(=O)[O-].[NH4+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m5_m2_m3:C(C)O, amount is: 0.0 ;m1_m4_m5_m2_m3:O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=C(C=CC(=C1)F)C(=NO)C1CN(CC1)CC1=CC=CC=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To the compound (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone (22 g) in 95% ethanol (350 ml) and water (100 ml) was added NH2OH.HCl (10.1 g) and ammonium acetate (12.7 g, 2.1 eq). The resulting mixture was refluxed for 3.5 hours. The mixture was then allowed to stir at room temperature for 24 hours. The reaction mixture was concentrated to remove ethanol, poured into water (500 ml), and extracted with dichloromethane (500 ml). This was followed by washing with water, brine, and drying over magnesium sulfate. The product was concentrated to an oil and purified by column chromatography to yield 12 g of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m7:FC1=C(C=CC(=C1)F)C(=NO)C1CN(CC1)CC1=CC=CC=C1, amount is: 0.0 ;m1_m2_m3_m7:[OH-].[K+], amount is: 0.0 ;m1_m2_m3_m7:O, amount is: 0.0 ;m4_m6:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m7:C(C)O, amount is: 0.0 ;m5:C(C)O, amount is: 0.0 MOLE;m4_m6:C(C)O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CN(CC2)CC2=CC=CC=C2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime (10.8 g, 34.2 mmol), potassium hydroxide (10 g), water (100 ml), and ethanol (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the solution was cooled and ethanol was removed on a rotary evaporator. The aqueous mixture was diluted with water (100 ml) then extracted with dichloromethane (500 ml). The organic solution was washed with brine and dried over anhydrous MgSO4. The solution was concentrated to an oil (9.8 g). The crude product was purified by flash chromatography over a silica gel column. The product thus obtained weighed 4.46 g (44%) as a light yellow oil. The oily product was dissolved in ethanol, and then treated with a solution of fumaric acid (1.73 g, 1.0 eq) in ethanol. Crystallization took place slowly with the addition of isopropyl ether. Recrystallization from ethanol (15 ml) gave 4.6 g of 6-fluoro-3-[1-(phenylmethyl)-3-pyrrolidinyl]-1,2-benzisoxazole fumarate as white crystals, m.p.=142°-144° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m5_m6_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5_m6_m4:Cl.ClCCCN1CCCCC1, amount is: 0.0 ;m1_m2_m3_m5_m6_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5_m6_m4:O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m5_m6_m4:C(C)#N, amount is: 0.0 ,Catalysts are m1_m2_m3_m5_m6_m4:S(=O)(=O)(O)[O-].C(CCC)[N+](CCCC)(CCCC)CCCC, amount is: 0.0 .Products are 0:C(\C=C\C(=O)O)(=O)O.C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCN2CCCCC2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 g, 13.6 mmol), N-(3chloropropyl)piperidine hydrochloride (4.05 g, 20.4 mmol), K2CO3 (6 g, 43.4 mmol), tetrabutylammonium hydrogen sulfate (phase transfer catalyst, 2.3 g) in acetonitrile (100 ml) and water (15 ml) was heated at reflux for 16 hours. The mixture was washed with brine and the layers were separated. The organic solution was concentrated. The crude product (6.4 g) was purified by flash chromatography over a silica gel column (55 g, sorbsil C-30; eluted with 2% CH3OH:0.5% DEA in DCM, 1.41). The oil thus purified (4.5 g) was treated with fumaric acid (1.6 g) in ethanol. The solid was collected: weight 3.1 g, m.p.178°-181° C. Recrystallization from ethanol yielded 2.28 g of white crystals, m.p.=190°-192° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC=1C=C2C=CNC2=CC1, amount is: 0.0 ;m1_m2_m3_m4:CC#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C3C=CNC3=CC2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.6 g, 11.8 mmol), K2CO3 (1.6 g, 11.6 mmol), KI (200 mg), 5-(3-chloropropoxy)indole (2.2 g, 10.5 mmol) and CH3CN (100 ml) was stirred at reflux under N2 for 18 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The EtOAc extract was washed 2 times with H2O, 2 times with brine and after drying with MgSO4 the solvent was removed in vacuo to yield 5.1 g of a dark oil. The oil was purified by preparative HPLC (Water's Associates Prep LC/System 500, using 2 silica gel columns and 4% MeOH-CH2Cl2 as eluent) to afford 2.65 g (65%) of a beige solid. Recrystallization from ethanol gave 2.2 g (54%) of a beige powder, m.p.=118°-121° C. |
Here is a chemical reaction formula: Reactants are m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C2C=CNC2=CC=C1, amount is: 0.0 ;m1_m2_m3_m4:CC#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m6:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C3C=CNC3=CC=C2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.5 g, 16 mmol), K2CO3 (2.2 g, 16 mmol), KI (200 mg), 4-(3-chloropropoxy)indole (3.0 g, 14 mmol) and CH3CN (100 ml) was stirred at reflux under N2 for 7 hours and then at ambient temperature for 68 hours. Reflux was resumed for an additional 6 hours whereupon a TLC revealed incomplete reaction. K2CO3 (0.5 g, 4 mmol) was added and the reaction was stirred at reflux for 17 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The organic extract was washed with H2O and saturated NaCl and after drying over MgSO4 the solvent was removed to afford 5.7 g of a beige solid. The product was purified by preparative HPLC (Water's Associates Prep LC/System 500 using 2 silica gel columns and 4% MeOH-CH2Cl2 as eluent) to yield 3.4 g (61%) of a beige solid. Two consecutive recrystallizations from EtOH provided 2.3 g (41%) of a white powder, m.p.=129°-131° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NS2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)O, amount is: 0.0 ;m1_m2_m3_m4:C(=O)(O)[O-].[Na+], amount is: 0.0 ;m1_m2_m3_m4:CC#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NS2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisothiazole (2.4 g, 10.1 mmol), 1-[4-(3-chloropropoxy)-3-hydroxyphenyl]ethanone (2.5 g, 11.1 mmol), NaHCO3, (0.94 g, 11.1 mmol), KI (100 mg) and CH3CN (100 ml) was stirred at reflux under N2 for 65 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The EtOAc extract was washed with H2O (1×) and brine (3×) and after drying with MgSO4 the solvent was evaporated to give 4.2 g of a dark solid. Three consecutive recrystallizations from EtOH provided 2.1 g (48%) of glittery beige crystals m.p.=135°-137° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4_m5_m6:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4_m5_m6:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4_m5_m6:BrCC(CO)(C)C, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4_m5_m6:O, amount is: 0.0 ;m1_m2_m3_m4_m5_m6:C(C)#N, amount is: 0.0 ,Catalysts are m1_m2_m3_m4_m5_m6:S(=O)(=O)(O)[O-].C(CCC)[N+](CCCC)(CCCC)CCCC, amount is: 0.0 .Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CC(CO)(C)C)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 g, 13.6 mmol), K2CO3 (12.5 g, 17.5 mmol), 3-bromo-2,2-dimethyl-1-propanol (3 g, 21 mmol, 1.5 eq.), tetra-butylammonium hydrogen sulfate (1 g, phase transfer catalyst) in water (5 ml) and acetonitrile (150 ml) was heated at reflux for 43 days. TLC showed a small spot for the expected product. The mixture was diluted with EtOAc (400 ml) and washed with brine. The organic solution was dried and concentrated to a dark brown mixture. The crude mixture was purified carefully by flash chromatography (SiO2, 95 g to afford the dried pure product; 260 mg, (6%) as an oil. This oil was converted to the fumarate salt by treatment with fumaric acid (98.5 mg, 1.0 eq.) in ethanol. Recrystallization from ethanol:ether yielded 210 mg of white crystals, m.p.=144°-145° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m4:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C=3C(C2=O)=CC=CC3)=O)C=C1, amount is: 0.0 ;m2:[BH4-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3_m4:CO, amount is: 0.0 ;m1_m3_m4:C(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2O)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a suspension of N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]phthalimide (7.8 g, 19.8 mmol) in methanol (250 ml) and DCM (30 ml) was added NaBH4 (1.7 g, 45.5 mmol) at room temperature under nitrogen. After stirring for 0.5 hours the homogeneous reaction mixture was concentrated. The remaining solid was purified on a flash chromatography column (SiO2, 1:1 EtOAc/DCM, increased to 10% MeOH) to give 7.0 g (90%) of the desired product as a solid which was recrystallized from EtOAc, m.p.=172°-173° C. |
Here is a chemical reaction formula: Reactants are m3:C(C)[SiH](CC)CC, amount is: 0.0 ;m1_m2_m5:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2O)=O)C=C1, amount is: 0.0 ;m1_m2_m5:FC(C(=O)O)(F)F, amount is: 0.0 ;m4:C(=O)(O)[O-].[Na+], amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m1_m2_m5:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2,3-dihydro-3-hydroxy-1H-isoindol-1-one (2.2 g, 5.6 mmol) was added a solution of trifluoroacetic acid (11.0 ml) in dichloromethane (30 ml) at room temperature, under nitrogen. Triethylsilane (1.5 ml) was then added and the reaction mixture was allowed to stir for 18 hours at which time it was poured into a NaHCO3 (sat.). The layers were separated and the aqueous phase was extracted with DCM (3×). The combined organics were washed with brine and dried (Na2SO4). Filtration and concentration gave the crude product as a solid which was recrystallized from EtOAc to give 1.6 g (79%) of the desired product as a white solid, m.p.=166°-168° C. |
Here is a chemical reaction formula: Reactants are m3:CCOCC, amount is: 0.0 ;m2:Cl, amount is: 0.0 MOLE;m1:FC1=CC=C2C(=NNC2=C1)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m4:CO, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:Cl.FC1=CC=C2C(=NNC2=C1)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A 5.0 g sample of N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]- ethyl]phthalimide was suspended in methanol (130 ml) and was made acidic with ethereal-HCl. After stirring for 1 hour, anhydrous ether (100 ml) was added and the suspension was stirred for an additional 30 minutes. The solid was collected and dried to afford 4.5 g of an off-white powder. This was combined with an additional sample (7.3 g total) and recrystallization from MeOH gave 4.3 g of the salt as an off-white powder, mp=265°-268° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCC(=O)OCC)C=C1, amount is: 0.0 ;m1_m3_m2:C(C)[Mg]Br, amount is: 0.0 ;m1_m3_m2:C1CCOC1, amount is: 0.0 ,this reaction does not need reagents,this reaction does not need solvents,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCC(CC)(CC)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propionate (3.9 g, 12.0 mmol) in THF (100 ml) was added ethylmagnesium bromide (12.0 ml, 36.0 mmol, 3.0M in ether) at room temperature under nitrogen (mild exotherm). The reaction mixture was stirred for 17 hours at which time it was carefully quenched with NH4Cl (sat., 20 ml). The precipitated salts were dissolved into water (25 ml) and the layers were separated. The aqueous phase was extracted with EtOAc (2×) and the combined organics were washed with brine and dried (Na2SO4). Filtration and concentration gave the crude product which was purified via flash column chromatography (silica gel, 1% MeOH/DCM) to give 2.4 g (61%) of the desired product as an oil which solidified on standing, m.p.=50°-53° C. |
Here is a chemical reaction formula: Reactants are m1_m4_m2:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2O)=O)C=C1, amount is: 0.0 ;m1_m4_m2:CCN(CC)CC, amount is: 0.0 ;m3:C(CCCCCCCCC)(=O)Cl, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m1_m4_m2:C(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2=O)OC(CCCCCCCCC)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl-2,3-dihydro-3-hydroxy-1H-isoindol-1-one (1.4 g, 3.5 mmol) in DCM (30 ml) was added Et3N (1.2 ml, 8.8 mmol) followed by decanoyl chloride at 0 C. under nitrogen. After stirring for 1 h in the cooling bath, the solvent was removed using a stream of nitrogen. The remaining residue was diluted with EtOAc and the precipitated triethylamine hydrochloride was filtered off. The filtrate was concentrated and the remaining oil was flushed through alumina with ether to give 1.6 g (83%) of the desired product as a yellow oil. |
Here is a chemical reaction formula: Reactants are m1_m4_m2:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCC(CC)(CC)O)C=C1, amount is: 0.0 ;m1_m4_m2:C(CCCCCCCCC)(=O)Cl, amount is: 0.0 ;m3:C(=O)(O)[O-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2:C(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:Cl.C(C)C(CCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F)(CC)OC(CCCCCCCCC)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 6-fluoro-3-[1-(3-hydroxy-3-ethylpentyl)-4-piperidinyl]-1,2-benzisoxazole (2.5 g, 7.48 mmol) in DCM (100 ml) was added decanoyl chloride (1.5 ml, 7.48 mmol) at 0° C., under nitrogen. The reaction mixture was stirred for 4 days at which time it was poured into NaHCO3 (sat., 50 ml). The layers were separated and the aqueous phase was extracted with DCM (2×). The combined organics were dried, filtered and concentrated to give the crude product which was purified via flash column chromatography (silica gel, 20-40% EtOAc/DCM). The product containing fractions were concentrated to give 3.0 g (81%) of the desired product as a yellow oil. The hydrochloride salt was prepared in anhydrous ether (60 ml) and isopropanol (1 ml) with ethereal HCl. The white salt was filtered and washed with anhydrous ether, m.p.=159°-161° C. |
Here is a chemical reaction formula: Reactants are m3:C(C)N(CC)CC, amount is: 0.0 MOLE;m4:Cl, amount is: 0.0 MOLE;m1_m5_m2:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2(C)O)=O)C=C1, amount is: 0.0 ;m1_m5_m2:Cl.CCOCC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m5_m2:C(Cl)(Cl)Cl, amount is: 0.0 ;m7_m6_m0:C(C)O, amount is: 0.0 MOLE;m7_m6_m0:CCOCC, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:Cl.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCN2C(C3=CC=CC=C3C2=C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To the solution of 2,3-dihydro-2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-3-hydroxy-3-methyl-1H-isoindol-1-one (4.88 g, 11.9 mmol) in chloroform (50 ml) was added HCl ether (1M, 20 ml) solution. A precipitate formed. This mixture was stirred for 18 hours at room temperature. The mixture was basified with triethylamine and washed with brine. The organic solution was dried and concentrated to a crude material. The purification was done by flash chromatography over silica gel column (SiO2, 60 g; eluted with DCM). The pure product thus obtained weighed 3.28 g (70%). Treatment with HCl.ether solution in ethanol gave 1.52 g of white crystals, m.p.=261°-263° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:C(Br)C1CO1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.O1C(CN2CCC(CC2)C2=NOC3=C2C=CC(=C3)F)C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (11 g, 50 mmol), K2CO3 (7.5 g, 54 mmol) and epibromohydrin (9 g, 54 mmol) in acetonitrile (150 ml) was heated at reflux for 16 hours. The mixture was filtered and concentrated to dryness. The crude product was purified by flash chromatography (SiO2, 180 g, eluted with methylene chloride (DCM), and 1-2% CH3OH in DCM). The material thus purified as off-white solids weighed 8.7 g (63%). This material (3 g) was converted to fumarate salt in ethanol and isopropyl ether to give 3.27 g of white crystals, m.p.=145°-147° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3:O1C(COC2=C(C=C(C=C2)C=O)OC)C1, amount is: 0.0 ;m1_m2_m3:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3:C(C)(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CC(COC2=C(C=C(C=C2)C=O)OC)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 4-(2,3-epoxypropoxy)-3-methoxyphenyl methanone (4.5 g, 22.5 mmol) and 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (5.36 g, 24.3 mmol) in isopropyl alcohol (150 ml) was heated at 55° C. for 16 hours. The mixture was cooled and the solvent was removed on a rotary evaporator. The residue was purified by at flash chromatography over a silica gel column (SiO2 ; 80 g; eluted with dichloromethane, DCM, and 1% CH3OH in DCM). The oil thus obtained solidified quickly, weight: 9.47 g. Recrystallization from ethanol and isopropyl ether, then toluene provided 8.6 g (86%) of white crystals, m.p.=107°-108° C. |
Here is a chemical reaction formula: Reactants are m1_m2:ClC(=O)OCCCCCCCCCC, amount is: 0.0 ;m1_m2:FC1=CC=C2C(=NNC2=C1)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m3:CCOCC, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:Cl.C(CCCCCCCCC)ON1N=C(C2=CC=C(C=C12)F)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of decanyl chloroformate (2.4 g, 11 mmol), and N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]ethyl]phthalimide (3.9 g, 10 mmol) was warmed on the steam bath for 15 minutes. The reaction was allowed to cool to ambient temperature, and then ether was added to the residue. The resulting solid was filtered to afford N-[2-[4-(1-decanoxy-6-fluoro-1H-indazol-3-yl)-1-piperazinyl]ethyl]phthalimide hydrochloride. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:COC1=C(C=C(C=C1)OC)O, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:CC(=O)C, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCOC1=C(C=CC(=C1)OC)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 2,5-dimethoxyphenol (29 g, 0.19 mol), K2CO3 (35 g), 3-chlorobromopropane (38.5 g, 0.25 mol) and acetone (250 ml) was stirred and refluxed for 6 hours, and then stirred at ambient temperature for 16 hours. The reaction was filtered, and the filtrate was concentrated to an orange liquid. The liquid was taken up into Et2O, and the organic layer washed with 1N NaOH, H2O, dried (MgSO4) and was concentrated to yield 37.8 g of an orange solid. An 11.7 g sample of this solid was flash chromatographed on silica gel (180 g) with 5% EtOAc/CH2Cl2 as eluent. Concentration of similar fractions gave 7.2 g of white, waxy solid, which was recrystallized from petroleum ether to afford a white solid, m.p. 48°-50° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=CC(=C(C=C1OC)C(C)=O)O, amount is: 0.0 ;m1_m2_m3_m4:C(=O)(O)[O-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=CC(=C(C=C2OC)C(C)=O)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.2 g, 19 mmol), 1-[4-(3-chloropropoxy)-2-hydroxy-5-methoxyphenyl]ethanone (5.0 g, 19 mmol), NaHCO3 (1.8 g, 20 mmol) and acetonitrile (120 mL) was stirred and refluxed for 16 hours. The reaction was filtered and the filtrate was concentrated to a dark oil. The oil was taken up in anhydrous ether and ethereal HCl was added to precipitate 8.7 g of an off-white hydrochloride salt. A 2.0 g sample of the salt was converted to its free base and chromatographed by preparative HPLC (silica gel with 5% MeOH/CH2 Cl2 as eluent). Concentration of the desired fractions gave 1.1 g of a white solid, which was recrystallized from EtOH to yield 0.85 g of the product, m.p. 122°-124° C. |
Here is a chemical reaction formula: Reactants are m1_m2:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2:C(C)(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CC(CC)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 4-(6-fluoro-1,2-benzisoxazol-3yl)piperidine (5.5 g, 25 mmol) and 1,2-expoxybutane (1.89 g, 26.3 mmol) in isopropyl alcohol (100 ml) was heated at 65° C. for 2 days. This mixture was cooled and the solvent was removed to leave a brown oil which was purified by flash chromatography over a silica gel column (SiO2, 70 g; eluted with DCM, 1 l and MeOH:DCM 2%:98%) to give an off-white solid weighing 6.3 g. Recrystallization from hot ethanol yielded 1.96 g of fine crystals, m.p. 87°-88° C. |
Here is a chemical reaction formula: Reactants are m1_m5_m2_m3_m4_m6:N(=NC(=O)OCC)C(=O)OCC, amount is: 0.0 ;m1_m5_m2_m3_m4_m6:FC1=CC2=C(C(=NO2)C2CCN(CC2)C(CO)CC)C=C1, amount is: 0.0 ;m1_m5_m2_m3_m4_m6:C1(C=2C(C(N1)=O)=CC=CC2)=O, amount is: 0.0 ;m1_m5_m2_m3_m4_m6:C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m5_m2_m3_m4_m6:C1CCOC1, amount is: 0.0 ;m1_m5_m2_m3_m4_m6:C1CCOC1, amount is: 0.0 ;m7:CCOCC, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)C(CN2C(C=3C(C2=O)=CC=CC3)=O)CC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of diethyl azodicarboxylate (DEAD, 4.9 g, 28.3 mmol) in THF (50 ml) was added dropwise to a solution of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butanol (6.9 g, 23.6 mmol), phthalimide (4.16 g, 1.2 eq), and triphenylphosphine (7.4 g, 28.3 mmol) in THF (200 ml) at room temperature. The solution was stirred at room temperature for 24 hours. After the reaction, the solvent was stripped to dryness. The residue was stirred in ether (200 ml) and the insolubles were removed by filtration. The oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g, eluted with dichloromethane, DCM, and 1-2% CH3OH in DCM) and (100 g of SiO2 ; eluted with DCM, 1 l, and 1% CH3OH in DCM, 1.2 l). Two close compounds were separated and the top compound on TLC (1.6 g) was recrystallized from isopropyl ether to yield 0.76 g of white crystals, m.p. 86°-88° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:C(C1=CC=CC=C1)(=O)N1N=C(C2=CC=C(C=C12)F)C1CCN(CC1)C, amount is: 0.0 ;m1_m3_m2:ClC(=O)OC1=CC=CC=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3_m2:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(C1=CC=CC=C1)(=O)N1N=C(C2=CC=C(C=C12)F)C1CCN(CC1)C(=O)OC1=CC=CC=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 1-benzoyl-6-fluoro-3-(1-methyl-4-piperidinyl)-1H-indazole (2.0 g, 5.93 mmol) in dichloromethane (100 ml) was added phenyl chloroformate (3.9 ml, 29.65 mmol) at room temperature. The reaction mixture was stirred at room temperature for 24 hours, refluxed for an additional 0.5 hours and subsequently concentrated. The remaining residue was dissolved into dichloromethane and washed with 10% HCl (aq.). The organic phase was dried (MgSO4), filtered, and concentrated to give an oil which was purified via flash column chromatography (silica gel, 20% DCM/EtOAc). Concentration of the product-containing fractions gave an oil which solidified on standing. The white solid was washed with EtOAc, leaving 0.47 g of the desired product, m.p. 137°-139° C. |
Here is a chemical reaction formula: Reactants are m3:ClCC#N, amount is: 0.0 ;m4:C(Cl)Cl.CCOC(=O)C, amount is: 0.0 MOLE;m1_m2_m5:FC1=CC=C2C(=NNC2=C1)C1CCNCC1, amount is: 0.0 ;m1_m2_m5:C(=O)(O)[O-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m5:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CC#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred suspension of 4-(6-fluoro-1H-indazol-3yl)piperidine (4.95 g, 22.6 mmol) and NaHCO3 (2.1 g, 24.9 mmol) in dry acetonitrile (110 ml) was added chloroacetonitrile (1.6 ml, 24.9 mmol) at room temperature, under nitrogen. The suspension was warmed to reflux for 22.5 hours, cooled to room temperature, and subsequently filtered. The remaining solids were washed with DCM and the combined filtrates were concentrated. The resulting brown oil was dissolved into EtOAc and washed with water. The organic phase was dried (MgSO4), filtered and concentrated to give a brown solid which was re-dissolved into DCM/EtOAc and flushed through alumina with DCM. The eluent was concentrated to give 5.2 g of the desired product as a solid, m.p. 149°-151° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CC#N, amount is: 0.0 ;m1_m3_m2:[H-].[Al+3].[Li+].[H-].[H-].[H-], amount is: 28.399999618530273 MILLIMOLE,this reaction does not need reagents,Solvents are m1_m3_m2:C1CCOC1, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CCN, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of [4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]-acetonitrile (6.1 g, 23.6 mmol) in dry THF (235 ml) was added (dropwise) lithium aluminum hydride (LAH) (28.4 mmol, 1.0M in THF) at room temperature, under nitrogen. Upon complete addition, the reaction mixture was warmed to reflux for 3 hours. After cooling to 0° C. in an ice bath, the reaction was carefully quenched with water (4.0 ml). The solids were removed via filtration and washed with THF. The combined filtrates were concentrated to give 5.6 g of the desired product. This material was suspended in DCM and filtered to give the product as an off-white solid, m.p. 125°-128° C. |
Here is a chemical reaction formula: Reactants are m3:C(Cl)Cl.CO, amount is: 0.0 MOLE;m1_m4_m2:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CCN, amount is: 0.0 ;m1_m4_m2:FC=1C=C2C(C(=O)OC2=O)=CC1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2:CN(C)C=O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C/C(=O)O)(=O)O.FC=1C=C2C(C(=O)N(C2=O)CCN2CCC(CC2)C2=NNC3=CC(=CC=C23)F)=CC1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 2-[4-(6-fluoro-1H-3-indazolyl)-1-piperidinyl]ethylamine (6.1 g, 23.3 mmol) in DMF (230 ml) was added 4-fluorophthalic anhydride (4.2 g, 25.5 mmol) at room temperature under nitrogen. The reaction mixture was warmed to 80 C. for 2.5 hours at which time it was allowed to cool to room temperature. The DMF was removed under reduced pressure to give a brown oil which was dissolved into DCM/MeOH. Purification via flash column chromatography (silica gel, 2% MeOH/DCM) afforded 3.6 g of the desired product as a white solid. The maleate salt was prepared in methanol (75 ml) using maleic acid (2.1 eq.). The precipitated salt was collected via filtration and recrystallized from acetonitrile to give a white solid, m.p. 193°-195° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:C1(=CC=CC=C1)S(=O)(=O)N1N=C(C2=CC=CC=C12)N1CCN(CC1)C, amount is: 0.0 ;m1_m3_m2:ClC(=O)OC1=CC=CC=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3_m2:ClCCl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C1(=CC=CC=C1)S(=O)(=O)N1N=C(C2=CC=CC=C12)N1CCN(CC1)C(=O)OC1=CC=CC=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 1-benzenesulfonyl-3-(1-methyl-4-piperazinyl)-1H-indazole (2.1 g, 5.89 mmol) in dichloromethane (100 ml) was added phenyl chloroformate (3.8 ml, 29.45 mmol) at room temperature. The reaction mixture was warmed to reflux for 2 hours, cooled to room temperature, and concentrated. The residue was diluted with ethyl acetate, filtered and purified via flash column chromatography (silica gel, ethyl acetate). Concentration of the product containing fractions gave an oil which solidified on standing. The product was washed well with heptane to give 1.5 g of a white solid, m.p. 112°-114° C. |
Here is a chemical reaction formula: Reactants are m1_m4:C1(=CC=CC=C1)S(=O)(=O)N1N=C(C2=CC=CC=C12)N1CCN(CC1)C(=O)OC1=CC=CC=C1, amount is: 0.0 ;m3:Cl, amount is: 0.0 ;m2:[OH-].[K+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4:C(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:N1(CCNCC1)C1=NNC2=CC=CC=C12, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a suspension of 1-benzenesulfonyl-3-(1-phenoxycarbonyl-4-piperazinyl)-1H-indazole (31.3 g, 67.7 mmol) in ethanol (500 ml) was added 50% KOH (aq.) (100 g of KOH in 100 g H2O) at room temperature. The reaction mixture was warmed to reflux for 6.5 hours and cooled to room temperature. After adjusting the pH to about two using HCl (con., 120 ml), the volatiles were removed under reduced pressure. The remaining residue was diluted with water and removed via filtration. The aqueous filtrate was washed with EtOAc and basified to pH=8 using 50% NaOH (aq.). The product was extracted into 10:1 dichloromethane/isopropylalcohol. The combined organics were dried (MgSO4), filtered, and concentrated to give 13.0 g of desired 3-piperazin-1-yl-1H-indazole as a brown solid which was used without further purification. |
Here is a chemical reaction formula: Reactants are m3:ClCC#N, amount is: 0.0 ;m1_m2_m4:N1(CCNCC1)C1=NNC2=CC=CC=C12, amount is: 0.0 ;m1_m2_m4:C(=O)(O)[O-].[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:N1N=C(C2=CC=CC=C12)N1CCN(CC1)CC#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred suspension of 3-piperazin-1-yl-1H-indazole (6.0 g, 29.7 mmol) and NaHCO3 (2.7 g, 32.7 mmol) in dry acetonitrile (125 ml) was added chloroacetonitrile (2.1 ml, 31.2 mmol) at room temperature, under nitrogen. The suspension was warmed to reflux for 17.5 hours, cooled to room temperature, and subsequently filtered. The remaining solids were washed with dichloromethane and the combined filtrates were concentrated. The resulting brown oil was purified via flash column chromatography (silica gel, 0-50% EtOAc/DCM) to give 4.0 g of product as an off-white solid, m.p. 121°-123° C. |
Here is a chemical reaction formula: Reactants are m3:C(C)O, amount is: 0.0 ;m1_m2:FC1=CC=C2C(=NNC2=C1)N1CCN(CC1)CCN1C(C2=CC=CC=C2C1=O)=O, amount is: 0.0 ;m1_m2:C(C1=CC=CC=C1)(=O)Cl, amount is: 0.0 ,this reaction does not need reagents,Solvents are m4:CCOCC, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:Cl.C(C1=CC=CC=C1)(=O)N1N=C(C2=CC=C(C=C12)F)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 2-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]ethyl]-1H-isoindol-1,3-(2H)-dione (6.0 g, 15 mmol) and benzoyl chloride (25 ml) was stirred at 175° C. under N2 for 2.0 hours. The reaction was cooled and diluted with anhydrous Et2O and the resultant hydrochloride salt was collected to yield 7.2 g. The compound was stirred in boiling absolute ethanol (300 ml) for 1 hour and then at ambient temperature overnight. The solid was collected and dried to afford 6.9 g. Recrystallization from MeOH gave 3.9 g of a light grey solid, m.p. 257°-260° C. |
Here is a chemical reaction formula: Reactants are m3:BrC(C=1C(=CC=CC1)C)Br, amount is: 0.0 ;m1_m2_m5:NC1CN(CCC1C1=NOC2=C1C=CC(=C2)F)CC(C)O, amount is: 0.0 ;m1_m2_m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m5:C(C)#N, amount is: 0.0 ;m4_m7:Cl, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m6:C(C)O, amount is: 0.0 MOLE;m4_m7:C(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:Cl.Cl.FC1=CC2=C(C(=NO2)C2CCN(CC2)CC(CN2CC3=CC=CC=C3C2)O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred mixture of 1-(3-amino-2-hydroxypropyl-4-(6-fluoro 1,2-benzisoxazol-3-yl)piperidine (2.24 g, 7.6 mmol), K2CO3 (1.61 g, 11.7 mmol) in acetonitrile (100 ml) was added α, α-dibromo-o-xylene (1.54 g, 6.1 mmol). The mixture was heated at reflux for 4 hours then cooled. The insolubles were filtered. The dark red solution was concentrated down. The residue was purified by flash chromatography over s silica gel column (SiO2, 30 g; eluted with 1% CH3OH in dichloromethane). The product so obtained weighed 940 mg as an oil. This oil was dissolved in ethanol and was treated with a solution of HCl in ethanol (188 mg of AcCl in ethanol). The dark solids were collected and recrystallized again in ethanol to yield off-white crystals (1.01 g), m.p. 240°-243° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCC(=O)N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CC(=O)N)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (6.77 g, 30.7 mmol), K2CO3 (5 g, 36.2 mmol) and 2-bromoacetamide (4.46 g, 32.3 mmol) in acetonitrile (250 ml) was heated to reflux for 4 hours. The insolubles were filtered and rinsed with dichloromethane (DCM). The solvents were removed. The residual solid was dissolved in DCM and upon concentration of this solution, 2.3 g of product crystallized out and was collected when the volume was reduced to about 50 ml. The rest of the product in DCM was purified by flash chromatography over a silica gel column (80 gm, SiO2 ; eluted with DCM and 1% CH3OH in DCM). The total product (4.2 g) thus purified was recrystallized from ethanol to yield 2.82 g of white crystals, m.p. 170°-172° C. dec. |
Here is a chemical reaction formula: Reactants are m1:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CCN, amount is: 0.0 ;m2:FC=1C=C2C(C(=O)OC2=O)=CC1, amount is: 0.0 ;m3:C(Cl)Cl.CO, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m4:CN(C)C=O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC=1C=C2C(C(=O)N(C2=O)CCN2CCC(CC2)C2=NNC3=CC(=CC=C23)F)=CC1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution consisting of 2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethylamine (6.1 g, 23.2 mmol) in DMF (230 ml) was added 4-fluorophthalic anhydride (4.2 g, 25.5 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to 80° C. for 2.5 hours at which time it was allowed to cool to room temperature. The DMF was removed under reduced pressure (<0.5 mmHg, 55° C.) to give a brown oil which was dissolved into DCM/MeOH. Purification via flash column chromatography (silica gel, 2% MeOH/DCM) afforded 3.6 g of 4-fluoro-N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]phthalimide. To a solution of the latter compound (3.6 g 8.8 mmol) in anhydrous THF (100 ml) was added LAH (18.4 ml of a 1.0M solution in THF, 18.4 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux for 4 hours. Upon cooling to room temperature, the reaction was quenched with water (1.5 ml, dropwise). The precipitated salts were removed via filtration and washed with DCM. The combined filtrates were concentrated to give a solid which was purified via flash column chromatography (silica gel, 0-8% MeOH/DCM). The product containing fractions were concentrated to give 2.4 g product as an off-white solid. The dimaleate salt was prepared in methanol using 2.4 eq. of maleic acid. The white precipitate was collected via filtration and washed with methanol, m.p. 186°-188 C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:N1N=C(C2=CC=CC=C12)N1CCNCC1, amount is: 0.0 ;m1_m2_m3_m4:BrCCN1C(C=2C(C1=O)=CC=CC2)=O, amount is: 0.0 ;m1_m2_m3_m4:C([O-])(O)=O.[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:N1N=C(C2=CC=CC=C12)N1CCN(CC1)CCN1C(C=2C(C1=O)=CC=CC2)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of 4-(1H-indazol-3-yl)piperazine (1.6 g, 7.9 mmol), N-(2-bromoethyl)phthalimide (2.1 g, 7.9 mmol), and sodium bicarbonate (0.7 g, 8.3 mmol) in acetonitrile (160 ml) was warmed to reflux for 24 hours. Upon cooling to room temperature, the reaction mixture was filtered through a pad of celite and the solids were washed with DCM. The combined filtrates were concentrated to give the N-[2-[4-(1H-indazol-3yl)-1-piperazinyl]ethyl]phthalimide which was used without further purification. |
Here is a chemical reaction formula: Reactants are m1_m2_m4_m3_m5:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m4_m3_m5:C(C)N(CC)CC, amount is: 0.0 ;m1_m2_m4_m3_m5:ClCC(=O)Cl, amount is: 0.0 ,this reaction does not need reagents,Solvents are m6:ClCCl, amount is: 0.0 ;m1_m2_m4_m3_m5:C(Cl)(Cl)Cl, amount is: 0.0 ;m1_m2_m4_m3_m5:C(Cl)(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCC(=O)N1CCC(CC1)C1=NOC2=C1C=CC(=C2)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (4.4 g, 20 mmol), triethylamine (2.1 g, 21 mmol) in chloroform (50 ml) was added to a solution of chloroacetyl chloride (2.5 g, 22 mmol) in chloroform (100 ml) dropwise at room temperature. The mixture was stirred for 2 hours. The solution was diluted with dichloromethane (DCM, 100 ml) and then washed with H2O and brine. The solvent was removed and the oily product was purified by flash chromatography (SiO2, 50 g; eluted with DCM and 1% CH3OH in DCM). The pure product was obtained as an oil, 4.2 g. Crystallization from ethanol yielded 2.2 g of white crystals, m.p. 101°-102° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:O1C(CN2CCC(CC2)C2=NOC3=C2C=CC(=C3)F)C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:Cl.COC=1C=C2CCNCC2=CC1OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)(C)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:COC=1C=C2CCN(CC2=CC1OC)CC(CN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 1-(2,3-epoxypropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl) piperidine (3.2 g, 11.6 mmol), K2CO3 (2 gm, 1.25 eq) and 6,7dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3.3 g, 1.25 eq) in isopropyl alcohol (200 ml ) was heated at reflux for 6 hours. The mixture was cooled and filtered. The solvent was removed to about 50 ml and the solution was allowed to stand overnight. Crystals (0.6 g) formed and were collected. The mother liquor was concentrated to a white solid. Recrystallization twice from ethanol yielded the product (1.95 g, m.p. 153°-154° C. |
Here is a chemical reaction formula: Reactants are m1_m4_m2_m3:FC1=CC=C2C(=NNC2=C1)C1CCNCC1, amount is: 0.0 ;m1_m4_m2_m3:BrCC(=O)N1CC2=CC=CC=C2CC1, amount is: 0.0 ;m1_m4_m2_m3:C([O-])(O)=O.[Na+], amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m4_m2_m3:CC#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C1N(CCC2=CC=CC=C12)C(CN1CCC(CC1)C1=NNC2=CC(=CC=C12)F)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 4-(6-fluoro-1H-indazol-3-yl)piperidine (4.8 g, 18.9 mmol) in CH3CN (200 ml) was added 2-bromo-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)ethanone (4.8 g, 18.9 mmol) and sodium bicarbonate (1.9 g, 22.7 mmol) at room temperature. The reaction mixture was warmed to reflux (4 hours), cooled to room temperature and filtered through a pad of celite. The solids were washed with DCM and the combined filtrates were concentrated. The remaining residue was purified via preparative HPLC (silica gel, 5-10% MeOH/DCM) to give 4.1 g of 1-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethanone which was used without as further purification. To a suspension of the latter (3.7 g, 9.4 mmol) in THF (100 ml) was added (dropwise) lithium aluminum hydride (11.3 ml of 1.0M solution in THF, 11.3 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux (5 hours), cooled to room temperature and carefully quenched with water (10 ml). The precipitated salts were removed via filtration and washed with 1:1 EtOAc/DCM. The combined filtrates were concentrated and the remaining oil was purified via flash column chromatography (silica gel, 10% MeOH/DCM) to give 2.2 g of the product. The dimaleate salt was prepared in methanol (30 ml) with maleic acid (3.0 eq.), m.p. 185°-187° C. |
Here is a chemical reaction formula: Reactants are m3_m5:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ;m1_m2:O1C(CN2CCC(CC2)C2=NOC3=C2C=CC(=C3)F)C1, amount is: 0.0 ;m1_m2:N1CCCC2=CC=CC=C12, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m4:C(C)(C)O, amount is: 0.0 ;m3_m5:C(C)O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)C(C(C)O)C2CNC3=CC=CC=C3C2)C=C1.FC1=CC2=C(C(=NO2)C2CCN(CC2)C(C(C)O)C2CNC3=CC=CC=C3C2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of N-(2,3-epoxypropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (2.41 g, 8.73 mmol), 1,2,3,4-tetrahydroquinoline (1.33 g, 10 mmol, in isopropyl alcohol (50 ml) was heated at reflux for 6 hours. The solution was cooled and the solvent was removed on a rotary evaporator. The crude solid was purified by flash chromatography over a silica gel column (SiO2, 40 g, eluted with methylene chloride DCM, and 1-3% MEOH in DCM). The product thus purified weighed 2.0 g. This material was dissolved in ethanol and was treated with a solution of fumaric acid (567 mg, 1.0 eq) in ethanol. The solids collected were recrystallized again from ethanol (50 ml) to yield 1.0 g of white crystals, as a hemifumarate, m.p. 170°-171° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCC#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCC#N)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (11 g, 50 mmol), K2CO3 (8.5 g, 74 mmol) and 3-bromopropionitrile (8.2 g, 1.2 eq) in acetonitrile (300 ml) was heated at reflux for 24 hours. The mixture was cooled and the insolubles were filtered. The solvent was removed on a rotary evaporator and the crude product was purified by flash chromatography over a silica gel column (SiO2, 120 g). The product thus purified weighed 8.94 g. Recrystallization from ethanol yielded the nitrile as white crystals 4.3 g, m.p. 100°-101° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3:FC1=CC=C2C(=NNC2=C1)N1CCNCC1, amount is: 0.0 ;m1_m2_m3:C(=O)(O)[O-].[Na+], amount is: 0.0 ;m1_m2_m3:CC#N, amount is: 150.0 MOLE,this reaction does not need reagents,Solvents are m4:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC=C2C(=NNC2=C1)N1CCN(CC1)CC#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperazinyl)-1-H-indazole (6.0 g, 2.7 mmol), NaHCO3 (2.5 g, 3.0 mmol) chloroacetonitrile (2.5 g, 3.3 mmol) and CH3CN (150 mol) was stirred at reflux under N2 for 18 hours. The cooled reaction was poured into H2O and the aqueous solution was extracted with EtOAc. The EtOAc extract was washed with H2O washed with brine, dried with MgSO4 and concentrated to yield 7.0 g of a tan solid. A 1.3 g sample was recrystallized from EtOAc to yield 0.65 g of a beige solid, m.p. 154°-156° C. |
Here is a chemical reaction formula: Reactants are m1_m3_m2:C1(=CC=CC=C1)S(=O)(=O)NN=C(C1=C(C=CC=C1)Br)Cl, amount is: 0.0 ;m1_m3_m2:CN1CCNCC1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3_m2:O1CCCC1, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C1(=CC=CC=C1)S(=O)(=O)NN=C(N1CCN(CC1)C)C1=C(C=CC=C1)Br, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution, under nitrogen, of α-chloro-2-bromobenzaldehyde phenylsulfonylhydrazone (271.1 g; 720 mmol) in tetrahydrofuran (THF; 2 L), was added dropwise N-methylpiperazine (159.7 g; 1600 mmol). The reaction was stirred at ambient temperature for three hours, and then permitted to stand at ambient temperature for 16 hours. The reaction was chilled in an ice bath, and then filtered to remove the piperazine hydrochloride that was formed. The filtrate was concentrated to yield a brown gum. The gum was triturated with hot acetonitrile, the mixture was cooled in an ice bath, and when cold, was filtered to remove unwanted side product. The filtrate was then concentrated to afford 392.9 g of a brown gum of crude 1-[[(phenylsulfon-yl)hydrazono]-(2-bromophenyl)methyl]-4-methylpiperazine. |
Here is a chemical reaction formula: Reactants are m2:[OH-].[Na+], amount is: 0.0 MOLE;m1_m3:N1N=C(C2=CC=CC=C12)N1CCN(CC1)C#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m3:OS(=O)(=O)O, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:N1(CCNCC1)C1=NNC2=CC=CC=C12, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 4-(1H-indazol-3-yl)-1-piperazinecarbonitrile (8.0 g, 40 mmol) and 25% H2SO4 (100 ml) was stirred at reflux for 4.5 hours. The reaction was cooled in an ice bath and made basic by the dropwise addition of 50% NaOH. The basic solution was extracted with ethyl acetate. The ethyl acetate was washed with H2O, dried with MgSO4, and concentrated to afford 5.2 g (73% of the desired compound, as a solid). The solid was recrystallized twice from toluene to afford 3.0 g of 3-(1-piperazinyl)-1-indazole, m.p.=153°-155° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:CN(C=O)C, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2 -benzisoxazole hydrochloride (5.1 g, 20 mmol), K2CO3 (5.2 g, 40 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (5.3 g, 22 mmol), and dimethylformamide (60 ml) was heated at 90° C. for 16 hours. The reaction was poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4) and concentrated to afford a moist solid. Recrystallization (twice) from ethyl alcohol afforded 5.0 g (58%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-ethanone as a beige solid, m.p.=118°-120° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCCOC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:CN(C=O)C, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCCOC2=C(C=C(C=C2)C(C)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (5.1 g, 0.02 mol), K2CO3 (5.2 g, 0.04 mol), 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (6.6 g, 22 mmol), and dimethylformamide (60 ml) was heated at 75° C. for 5 hours. The reaction was poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent was concentrated to yield initially an oil, which solidified upon standing. The solid was triturated with hexane and collected to afford 7.7 g of the product as a waxy solid. The compound was chromatographed on a Waters Prep 500 utilizing silica gel columns and eluting with dichloromethane/methanol (5%). Concentration of the appropriate fractions yielded 5.1 g of off-white solid 1-[4-[4-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-butoxy]-3-methoxyphenyl]ethanone, which when recrystallized from ethyl alcohol yielded 3.2 g (36%) of feathery-white needles, m.p.=88°-90° C. |
Here is a chemical reaction formula: Reactants are m6:C(=O)(O)[O-].[Na+], amount is: 0.0 MOLE;m3:B(Br)(Br)Br, amount is: 0.0 MOLE;m4:B(Br)(Br)Br, amount is: 0.0 MOLE;m1_m7_m2:ClCCCOC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ;m1_m7_m2:C(=O)=O.CO, amount is: 0.0 MOLE;m5:C(=O)(O)[O-].[Na+], amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m8:C(Cl)Cl, amount is: 0.0 ;m1_m7_m2:C(Cl)Cl, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:ClCCCOC1=C(C=C(C=C1)C(C)=O)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution of 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (10.0 g, 41 mmol) in methylene chloride (120 ml) cooled to -50° C. (dry ice-methanol) was added, dropwise, 1M boron tribromide in methylene chloride (123 ml, 120 mmol). The temperature was kept between -40° C. and -50° C. After complete addition, the reaction was permitted to reach -30° C., and the TLC checked (ca. 15 min. after final boron tribromide was added). Saturated NaHCO3 was added, dropwise, never allowing the temperature to go above 0° C. during most of the addition. When sufficient NaHCO3 had been added to make the solution basic, the organic layer was collected. The layer was washed with brine, dried (MgSO4), and concentrated to yield 8.1 g of dark brown oil, which solidified on standing. This was chromatographed on a Waters Prep 500 LC (2 silica columns, 2% methanol-methylene chloride as eluent). Upon concentration of the appropriate fractions, 5.8 g of a brown tacky solid were obtained. This was recrystallized from isopropyl ether (with decanting of the yellow isopropyl ether supernatant from the dark brown oily residue) to give initially 2.5 g of a yellow solid. Concentration of the mother liquor gave an additional 0.5 g, m.p.=110°-113° C. |
Here is a chemical reaction formula: Reactants are m4_m6:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ;m1_m2_m3_m5:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5:COC1=C(OCCCCl)C=CC=C1, amount is: 0.0 ,this reaction does not need reagents,Solvents are m4_m6:C(C)O, amount is: 0.0 ;m1_m2_m3_m5:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=CC=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.45 g; 11.1 mmol), K2CO3 (2.0 g), and 3-(2-methoxyphenoxy)propyl chloride (3.5 g, 17.4 mmol) in acetonitrile (40 ml) was heated at 90° C. for 4 hours. At the end of the reaction, the solvent was removed, and the solids were dissolved into dichloromethane (100 ml). The solution was washed with water and brine, then dried over MgSO4. The crude material from the solution was combined with 1.2 g of crude material prepared in the same fashion (using 0.5 g of starting material). The combined material was purified by flash chromatography on a silica gel column (49 g, eluted with 0.5% diethylamine: 1% methanol:98.5% dichloromethane, 1 L). The fractions containing the pure product were pooled and concentrated down to a light oil (3.68 g). This oil was treated with fumaric acid (1.14 g, 9.8 mmol) in ethanol (13 ml). The 6-fluoro-3-[1-[3-(2-methoxyphenoxy)-propyl]-4-piperidinyl]-1,2-benzisoxazole fumarate crystals obtained weighed 4.01 g (60%), m.p.=169°-170° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC=1C=C(C=CC1OC)C1(CC=CC=C1)C=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)C2(CC=CC=C2)C=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2 -benzisoxazole (2.01 g; 9.13 mmol), K2CO3 (2.0 g), and 1-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenylmethanone (3.93 g; 11.3 mmol) and acetonitrile (50 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was evaporated and the residue was partitioned between water (150 ml) and dichloromethane (400 ml). The dichloromethane solution was washed with water and brine (100 ml), dried over MgSO4 then concentrated to an oil. The purification was done by flash chromatography over a silica gel column (SiO2, 40 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 850 ml). The material thus obtained as a colorless oil solidified on standing. Recrystallization from ethanol (150 ml) gave 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]phenylmethanone as white crystals, 3.07 g (63%), m.p.=140°-141° C. |
Here is a chemical reaction formula: Reactants are m4:O, amount is: 0.0 ;m3:BrCCCBr, amount is: 0.0 ;m1_m5_m2:OC=1C=C(C(=O)C2=CC=CC=C2)C=CC1OC, amount is: 0.0 ;m1_m5_m2:[H-].[Na+], amount is: 0.0 ;m1_m5_m2:CN(C=O)C, amount is: 0.0 ,this reaction does not need reagents,this reaction does not need solvents,this reaction does not need catalysts,Products are 0:BrCCCOC1=C(C=CC(=C1)OC)C=1C=C(C=CC1)C=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of 3-hydroxy-4-methoxybenzophenone (4.6 g, 20 mmol) in dimethylformamide (35 ml) was treated with sodium hydride (600 mg, 25 mmol) at 0° C. for 20 minutes, then 1,3dibromopropane (5 g, 24.7 mmol) was added in one portion. The mixture was heated at 90° C. for 1 hour, and then stirred at room temperature for 2 hours. At the end of the reaction, the mixture was poured into water (500 ml) and extracted with ethyl acetate (400 ml). The ethyl acetate solution was washed with water, brine and dried over anhydrous MgSO4. The solvent was removed and the crude oil was purified by flash chromatography over a silica gel column (SiO2, 85 g; eluted with 3:1 hexane:dichloromethane, 1.6 l; 3:7 hexane: dichloromethane, 1.4 l). The pure product thus obtained weighed 4.67 g, (66%) as an oil. Recrystallization twice from isopropyl ether (500 ml) gave analytically pure 3-(3-bromopropoxy-4-methoxyphenyl)phenylmethanone (2.42 g), m.p.=81°-83° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC=1C=C(C=CC1)C(C)=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2)C(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.53 g, 20.5 mmol), K2CO3 (4.5 g), 1-[3-(3-chloropropoxy)phenyl]ethanone (6.4 g, 29 mmol) in acetonitrile (60 ml) was heated at reflux for 5 hours. At the end of the reaction, the solvent was removed and the residue was extracted into dichloromethane (300 ml). The inorganic insolubles were filtered off. The dichloromethane solution was concentrated to a small volume (10 ml) and purified on a flash chromatographic column (SiO2, 75 g, eluted with dichloromethane, 900 ml; and 2% methanol in dichloromethane, 800 ml). The fractions containing the pure product were combined and concentrated to an oil (2.87 g, 35%). The oil was dissolved into ethanol and treated with a solution of fumaric acid (841 mg). Recrystallization (twice) from ethanol afforded 2.53 g of 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone fumarate as white crystals, m.p.=172°-174° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4_m5:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4_m5:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4_m5:BrCCCOC1=C(C=C(C=C1)C)C(C)=O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4_m5:CN(C=O)C, amount is: 0.0 ;m1_m2_m3_m4_m5:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C)C(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (2.87 g, 11.23 mmol), K2CO3 (2.5 g), 1-[2-(3-bromopropoxy)-5-methylphenyl]ethanone (3.74 g, 13.8 mmol) in dimethylformamide (10 ml) and acetonitrile (50 ml) was heated at 95° C. for 6 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (300 ml). The organic solution was washed with water and brine, dried over MgSO4 then concentrated down to a crude oil. The purification was done by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% CH3OH:dichloromethane: 1.2 l; 3% CH3 OH:dichloromethane: 600 ml). The material thus obtained was crystallized from a small volume of ether and hexane to provide 2.13 g (46%) of off-white 1-[2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-5-methylphenyl]ethanone, m.p.=92°-93° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m5_m6:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5_m6:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5_m6:BrCCCOC=1C=C(C=CC1OC)NC(C)=O, amount is: 0.0 ;m4_m8:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ,this reaction does not need reagents,Solvents are m7:C(C)O, amount is: 0.0 MOLE;m1_m2_m3_m5_m6:CN(C=O)C, amount is: 0.0 ;m1_m2_m3_m5_m6:C(C)#N, amount is: 0.0 ;m4_m8:C(C)O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)NC(C)=O)C=C1.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC=2C=C(C=CC2OC)NC(C)=O)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.94 g, 15.4 mmol), K2CO3 (3.67 g, 26.6 mmole), N-[3-(3-bromopropoxy)-4-methoxyphenyl]acetamide (5.56 g, 18.6 mmol) in dimethylformamide (75 ml) and acetonitrile (100 ml) was heated at 100° C. for 3 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (500 ml). The organic solution was washed with water (500 ml) and brine (400 ml), dried, then concentrated to a crude oil. The purification was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3 OH:dichloromethane, 500 ml). The material thus obtained weighed 2.33 g (34.3%) as an oil. This material was dissolved in ethanol and treated with a solution of fumaric acid (661 mg) in ethanol. The N-[3-[3-[4-(6-fluoro-1,2 -benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate was obtained as off-white crystals weighing 2.17 g, m.p.=205°-206° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC=C2C(=NNC2=C1)C1CCNCC1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC=C2C(=NNC2=C1)C1CCN(CC1)CCCOC1=C(C=C(C=C1)C(C)=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1H-indazole (3.5 g, 16 mmol), K2CO3 (2.2 g), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (3.8 g, 16 mmol) and acetonitrile (90 ml) was refluxed for 16 hours. The reaction was poured into water and the resulting white solid, which precipitated from solution, was collected to afford 5.5 g of the desired product. The compound was recrystallized from dimethylformamide (twice) to afford 3.0 g (44%) of 1-[4-[3-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]propoxy]-methoxyphenyl]ethanone as a white solid, m.p.=202°-204° C. |
Here is a chemical reaction formula: Reactants are m4_m8:C(\C=C\C(=O)O)(=O)O, amount is: 0.0 ;m1_m2_m3_m5_m6:Cl.FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m5_m6:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m5_m6:BrCCCOC1=C(C=C(C=C1)C(C)=O)C, amount is: 0.0 ,this reaction does not need reagents,Solvents are m4_m8:C(C)O, amount is: 0.0 MOLE;m7:C(C)O, amount is: 0.0 MOLE;m1_m2_m3_m5_m6:CN(C=O)C, amount is: 0.0 ;m1_m2_m3_m5_m6:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:C(\C=C\C(=O)O)(=O)O.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)C)C=C1.FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)C)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.0 g; 11.7 mmol), K2CO3 (3.0 g), and 1-[4-(3-bromopropoxy)-3-methylphenyl]-ethanone (3.19 g) in dimethylformamide (20 ml) and acetonitrile (50 ml) was heated at 95° C. for 4 hours. At the end of the reaction, the solvent was concentrated down to about 30 ml, then partitioned between water (200 ml) and dichloromethane (300 ml). The dichloromethane solution was separated and washed with water and brine, then dried over MgSO4. The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml). The material thus obtained was a light yellow oil, weight: 2.07 g (43%). This oil was dissolved in ethanol and treated with a solution of fumaric acid (585 mg) in ethanol. The 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methylphenyl]ethanone hemifumarate crystals formed on cooling at 0° C. This was collected and weighed 1.5 g, m.p.=185°-187° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C#N)C=C1)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C#N)C=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), K2CO3 (2.8 g), 4-(3-bromopropoxy)-3-methoxybenzonitrile (4.0 g, 14.8 mmol) in acetonitrile (70 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was removed on a rotary evaporator. The organic material was extracted into dichloromethane (250 ml) and the inorganics were filtered off. The dichloromethane solution was concentrated to a crude oil. The purification was done by flash chromatography over a silica gel column (SiO2, 55 g; eluted with dichloromethane, 600 ml; 1% methanol in dichloromethane, 600 ml). The material thus obtained was crystallized from a small amount of dichloromethane. Recrystallization from ethanol (25 ml) provided 3.8 g (68%) of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzonitrile as white crystals, m.p.=107°-108° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1Br)C(C)=O)Br, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrC=1C=C(C=C(C1OCCCN1CCC(CC1)C1=NOC2=C1C=CC(=C2)F)Br)C(C)=O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.0 g, 9.0 mmol), K2CO3 (1.3 g), and 1-[4(3-bromopropoxy)-3,5-dibromophenyl]ethanone (2.65 g, 9.0 mmol) and acetonitrile (50 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was evaporated and the residue was extracted into dichloromethane (150 ml). The insolubles were filtered off. The dichloromethane solution was concentrated down to an oil. The purification was done by flash chromatography on a silica gel column (SiO2, 47 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 600 ml). The material thus purified as a colorless oil, solidified on standing. Recrystallization from ethanol gave 1-[3,5-dibromo-4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-phenyl]ethanone as white crystals (2.93 g, 57%), m.p.=102°-103° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=CC=CC=C1, amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 MOLE,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=CC=CC=C2)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.0 g, 18.2 mmol), K2CO3 (3.0 g, 21.8 mmol), KI (100 mg), 3-chloropropoxybenzene (3.4 g, 20.0 mmol), and acetonitrile was stirred at reflux under nitrogen for 30 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried with MgSO4 and concentrated to afford 6.2 g of a damp, beige solid. The compound was recrystallized twice from ethanol to yield (47%) of 6-fluoro-3-[1-(3-phenoxypropyl)-4-piperidinyl]-1,2-benzisoxazole as a light beige solid, m.p.=78°-80° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C(F)(F)F)=O)OC, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C(F)(F)F)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (1.5 g, 6.7 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone (2.0 g, 6.7 mmol), K2CO3 (0.88 g), KI (0.1 g) and acetonitrile (50 ml) was stirred and refluxed for 16 hours. After cooling, the reaction was poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed (H2O), dried (MgSO4), and the solvent was concentrated to an oil, which upon evacuation at high vacuum afforded 3.2 g of a waxy solid. The solid was chromatographed on a Waters preparative LC (silica columns, eluting with 3% methanol-dichloromethane). Concentration of the appropriate fractions gave 1.8 g (56%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoro-ethanone solid, m.p.=94°-96° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:CC(=O)C1=CC(=C(C(=C1)Br)O)Br, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCBr, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:BrCCCOC1=C(C=C(C=C1Br)C(C)=O)Br, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A stirred mixture of 3,5-dibromo-4-hydroxyacetophenone (3.0 g, 10.1 mmol), K2CO3 (2.8 g, 20.3 mmol), 1,3-dibromopropane (4.0 g, 19.8 mmol) in acetonitrile (100 ml) was heated at reflux for 5 hours. The solvent was removed. The crude product was extracted into dichloromethane (150 ml) and the insoluble inorganics were filtered off. The solution was concentrated to dryness again. Purification was carried out by flash chromatography on silica gel (45 g, SiO2 ; eluted with 1:1 hexane:dichloromethane). The material thus obtained (2.8 g) was recrystallized twice from isopropyl ether to give analytically pure 1-[4-(3-bromopropoxy)-3,5-dibromophenyl]ethanone, m.p.=87°-88° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1)CC(CCC)=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)CC(CCC)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10 mmol), K2CO3 (3 g), 1-[4-(3-bromopropoxy)-3-methoxyphenyl]pentanone (3.7 g, 11.3 mmol) in acetonitrile (140 ml) was heated at reflux for 4 hours. At the end of the reaction, the mixture was cooled and filtered. The filtrate was concentrated to an oil. Purification was performed by flash chromatography over a silica gel column (SiO2, 55 g; eluted with 1% methanol in dichloromethane, 600 ml; 3% methanol: 97% dichloromethane, 400 ml). The fractions containing pure product were pooled and concentrated to a solid (4.3 g, 91%). Recrystallization from ethanol (10 ml) gave a powdery solid of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-pentanone (3.22 g), m.p.=79°-80° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C=C1)CC(C)=O)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)CC(C)=O)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.8 g, 15.2 mmol), K2CO3 (3 g), 1-[4-(3-bromopropoxy)-3-methoxyphenyl]propanone (4.6 g, 18.2 mmol) in acetonitrile (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the mixture was filtered and the solvent was concentrated and the residue was extracted into dichloromethane (300 ml). The dichloromethane was filtered and concentrated again. The crude material (6.4 g) was purified by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 700 ml; 1% methanol in dichloromethane, 1.4 l). The material thus purified (weight: 2.87 g, 51%) was recrystallized from ethanol (25 ml) to give 2.13 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]propanone as beige colored crystals, m.p.=118°-119° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:BrCCCOC1=C(C=C(C(=O)N)C=C1)OC, amount is: 0.0 ,this reaction does not need reagents,Solvents are m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C(=O)N)C=C2)OC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10.0 mmol), K2CO3 (2.0 g) and 4-(3-bromopropoxy)-3-methoxybenzamide (2.32 g, 8.0 mmol) in acetonitrile (80 ml) was heated at reflux for 5 hours. At the end of the reaction the solvent was evaporated. The residue was extracted into dichloromethane. The inorganic insolubles were filtered off. The dichloromethane was concentrated again. The crude residue was purified by flash chromatography over a silica gel column (55 g, SiO2 ; eluted with 1% methanol in dichloromethane, 1 l; 2% methanol in dichloromethane, 1 l). The material thus obtained weighed 2.93 g (84%) as white crystals. Recrystallization from hot ethanol (60 ml) gave 2.2 g of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzamide as white crystals, m.p.=163°-164° C. |
Here is a chemical reaction formula: Reactants are m1_m2_m3_m4:FC1=CC2=C(C(=NO2)C2CCNCC2)C=C1, amount is: 0.0 ;m1_m2_m3_m4:C(=O)([O-])[O-].[K+].[K+], amount is: 0.0 ;m1_m2_m3_m4:ClCCCOC1=C(C=C(C=C1)C(C)=O)NC, amount is: 0.0 ;m1_m2_m3_m4:C(C)#N, amount is: 0.0 ,this reaction does not need reagents,Solvents are m5:O, amount is: 0.0 MOLE,this reaction does not need catalysts,Products are 0:FC1=CC2=C(C(=NO2)C2CCN(CC2)CCCOC2=C(C=C(C=C2)C(C)=O)NC)C=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.3 g, 10.3 mmol), K2CO3 (1.4 g, 10.3 mmol), 1-[4(3-chloropropoxy)-3-(methylamino)phenyl]ethanone (2.5 g, 10.3 mmol), KI (0.10 g), and acetonitrile (100 ml) was stirred at reflux under nitrogen for 23 hours. The reaction was cooled to ambient temperature, poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate yield 4.8 g of a damp, brown solid. The compound was isolated by preparative HPLC (Waters Associates prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent). Concentration of appropriate fractions afforded 2.4 g. Recrystallization from ethanol gave 2.1 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-(methylamino)phenyl]ethanone as a beige solid, m.p.=151°-153° C. |