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Here is a chemical reaction formula: Reactants are:m1_m2_m5:[Li]CCCC;m1_m2_m5:C(C)(C)NC(C)C;m3_m4:FC1=CC=C(C=N1)C12CCCN2CCC1;m3_m4:BrC(C(F)(F)Br)(F)F, Reagents are:m1_m2_m5:C1CCOC1, and Products are 0:BrC=1C=C(C=NC1F)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: n-BuLi (2.5M in hexanes, 0.252 mL, 0.63 mmol) was added to di-isopropylamine (0.082 mL, 0.63 mmol) in THF and stirred at room temperature for 10 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (123 mg, 0.60 mmol, from Example 12d) and 1,2-dibromo-1,1,2,2-tetrafluoroethane (0.215 mL, 1.80 mmol) were added. The mixture was slowly warmed to room temperature and stirred overnight. The reaction was quenched with 2N HCl, and the mixture was washed with Et2O. The aqueous layer was basified with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried, (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (64 mg, 37%). 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.79-2.06 (m, 6H), 2.64-2.72 (m, 2H), 3.12-3.19 (m, 2H), 8.14 (dd, J=8.8, 2.2 Hz, 1H), 8.19 (dd, J=2.2, 1.2 Hz, 1H); MS (CI/NH3) m/z: 285/287 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3:BrC=1C=C(C=NC1F)C12CCCN2CCC1;m4_m2:Cl, Reagents are:m1_m3:CCOCC;m4_m2:CCOCC, and Products are 0:Cl.BrC=1C=C(C=NC1F)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5-bromo-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (59 mg, 87%): mp 213°-215° C.; 1H NMR D2O, 300 MHz) δ2.15-2.49 (m, 6H), 2.56-2.65 (m, 2H), 3.34-3.42 (m, 2H), 3.78-3.87 (m, 2H), 8.31 (dd, J=2.4, 1.0 Hz, 1H), 8.38 (dd, J=7.8, 2.4 Hz, 1H); MS (CI/NH3) m/z: 285/287 (M+H)+; MS (CI/NH3): m/z 285/287 (M+H+). Anal. Calcd for C12H14BrFN2.HCl: C, 44.81; H, 4.70; N, 8.71. Found: C, 45.04; H, 4.25; N, 8.48. |
Here is a chemical reaction formula: Reactants are:m3_m4:FC1=CC=C(C=N1)C12CCCN2CCC1;m3_m4:ClC(C(Cl)(Cl)Cl)(Cl)Cl;m1_m2_m5:[Li]CCCC;m1_m2_m5:C(C)(C)NC(C)C, Reagents are:m1_m2_m5:C1CCOC1, and Products are 0:ClC=1C=C(C=NC1F)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: n-BuLi (2.5M in hexanes, 0.232 mL, 0.58 mmol) was added to di-isopropylamine (0.077 mL, 0.58 mmol) in THF and stirred at room temperature for 15 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.56 mmol, from Example 12d) and hexachloroethane (400 mg, 1.7 mmol) were added. The mixture was slowly warmed to room temperature and stirred overnight. The reaction was quenched with 2N HCl, and the mixture was washed with Et2O. The aqueous layer was basified with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried, (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (45 mg, 34%): 1H NMR (CDCl3, 300 MHz) δ1.60-1.72 (m, 2H), 1.80-2.06 (m, 6H), 2.64-2.72 (m, 2H), 3.14-3.27 (m, 2H), 8.00 (dd, J=8.8, 2.0 Hz, 1H), 8.15 (dd, J=2.0, 1.0 Hz, 1H); MS (CI/NH3) m/z: 241 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:ClC=1C=C(C=NC1F)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.ClC=1C=C(C=NC1F)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(5-chloro-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (35 mg, 74%): mp 181°-183° C.; 1H NMR (D2O, 300 MHz) δ2.15-2.50 (m, 6H), 2.56-2.65 2H), 3.34-3.42 (m, 2H), 3.79-3.87 (m, 2H), 8.24-8.29 (m, 2H); MS (CI/NH3) m/z: 241 (M+H)+ ; MS (CI/NH3): m/z 241/243 (M+H+). Anal. Calcd for C12H14 ClFN2.HCl: C, 52.00; H, 5.45; N, 10.11. Found: C, 51.81; H, 5.62; N, 9.84. |
Here is a chemical reaction formula: Reactants are:m1_m4:IC=1C=NC=CC1C;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12;m2_m5:[Li]C(C)(C)C, Reagents are:m1_m4:CCOCC;m2_m5:CCCCC, and Products are 0:CC1=C(C=NC=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 3-Iodo-4-methylpyridine (330 mg, 3.10 mmol) was dissolved in Et2O and cooled to -95° C. A solution of t-BuLi (1.7M in pentane, 4.0 ml, 6.80 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (960 mg, 4.60 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with stirring for 2 hours. The cold bath was removed, 2N HCl was added, and the phases were separated. The aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (41 mg, 6%): 1H NMR (CDCl3, 300 MHz) δ1.54-1.69 (m, 2H), 1.77-1.89 (m, 2H), 1.93-2.11 (m, 4H), 2.41 (s, 3H), 2.69-2.77 (m, 2H), 3.08-3.15 (m, 2H), 7.02 (d, J=4.8 Hz, 1H), 8.32 (d, J=4.8 Hz, 1H), 9.06 (s, 1H); MS (CI/NH3) m/z: 203 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:CC1=C(C=NC=C1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.Cl.CC1=C(C=NC=C1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 7a-(4-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (37 mg, 0.18 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white solid (26.2 mg, 61%): mp 244°-247° C.; 1H NMR D2O, 300 MHz) δ2.01-2.16 (m, 2H), 2.27-2.52 (m, 4H), 2.65 (s, 3H), 2.65-2.78 (m, 2H), 3.45-3.54 (m, 2H), 3.87-3.96 (m, 2H), 7.75 (d, J=5.6 Hz, 1H), 8.49 (s, 1H), 8.55 (d, J=5.6 Hz, 1H); MS (CI/NH3): m/z 203 (M+H+). Anal. Calcd for C13H18N2.2 HCl: C, 56.73; H, 7.32; N, 10.18. Found: C, 56.94; H. 7.24; N, 9.99. |
Here is a chemical reaction formula: Reactants are:m2:C1(=CC=CC=C1)B(O)O;m3:C([O-])([O-])=O.[Na+].[Na+];m1:BrC=1C=NC=C(C1)Br, Reagents are:m5:C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Pd];m4:C1(=CC=CC=C1)C, and Products are 0:BrC=1C=NC=C(C1)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Portions of 3,5-dibromopyridine (1.0 g, 4.22 mmol), phenylboronic acid (570 mg, 4.6 mmol) and palladium tetra(triphenylphosphine) (60 mg) were combined in toluene (20 mL) with aqueous sodium carbonate solution (2M, 3.0 mL) and heated at reflux for 6 hours. The mixture was cooled to ambient temperature, and the solvent was removed. The residue was purified by chromatography (silica gel, eluting with ether:hexane 1:10 to give the title compound: MS (CI/NH3) m/z: 234/236 (M+H)+, 251/153 (M+NH4)+ ; 1H NMR (CDCl3, 300 MHz) δ7.21-8.02 (dd, J=2.0, 2.0 Hz), 8.65 (d, J=2.0 Hz), 8.75 (d, J=2.0 Hz). |
Here is a chemical reaction formula: Reactants are:m1_m5:BrC1(CN=CC=C1)C1=CC=CC=C1;m4:Cl;m2_m6:[Li]C(C)(C)C;m3:Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12, Reagents are:m1_m5:CCOCC;m2_m6:CCCCC, and Products are 0:C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 3-Bromo-3-phenylpyridine (200 mg, 0.85 mmol) was dissolved in Et2O and cooled to -30° C. A solution of 2.5M t-BuLi (1.1 mL, 1.90 mmol) in pentane was added, and the reaction was stirred for 10 minutes. 1,2,3,5,6,7-Hexahydropyrrolizinium perchlorate (230 mg, 1.30 mmol) was added, and the reaction mixture was allowed to stir for 30 minutes at -30° C. then allowed to warm to room temperature and stir for 1 hour. Then 2N HCl was added, the phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The organic phases were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 95:5) to afford a clear oil (32.5 mg). |
Here is a chemical reaction formula: Reactants are:m4_m2:Cl;m1_m3:C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1, Reagents are:m4_m2:CCOCC;m1_m3:CCOCC, and Products are 0:Cl.C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The 7a-(5-phenyl-3-pyridinyl)-hexahydro-1H-pyrrolizine compound from step 25b was dissolved in ether (5 mL) and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was dried to afford the title compound as yellow needles (13.5 mg): mp 217°-220° C. (dec.); 1H NMR D2O, 300 MHz) δ2.17-2.47 (m, 4H), 2.57-2.73 (m, 4H), 3.41-3.50 (m, 2H), 3.87-3.97 (m, 2H), 7.60-7.68 (m, 3H), 7.75-7.81 (m, 2H), 8.60 (dd, J=2.0, 2.0 Hz, 1H), 8.87 (d, J=2.0 Hz, 1H), 9.04 (d, J=2.0 Hz, 1H); MS (CI/NH3) m/z: 265 (M+H)+. Anal. Calcd for C18H20N2.2.0 HCl.0.1 H2O: C, 63.76; H, 6.60; N, 8.26. Found: C, 63.62; H, 6.48; N, 8.02. |
Here is a chemical reaction formula: Reactants are:m1_m4:BrCCCCCC(=O)NCC(=O)OCC;m2:[C-]#N.[K+];m3:ClCCl, Reagents are:m1_m4:C(C)O, and Products are 0:C(#N)CCCCCC(=O)NCC(=O)OCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 23.73 g (84.7·10-3 mol) of N-(6-bromohexanoyl)-glycine, ethyl ester are dissolved in 200 ml of ethanol, and 6.5 g (0.1 mol) of powdered potassium cyanide are added. The reaction mixture is brought to the reflux point and stirred under reflux for 15 hours. After concentration of the mixture under reduced pressure, the residue is taken up with dichloromethane and the organic phase is washed with aqueous sodium chloride solution. The organic phase is dried and concentrated under reduced pressure to give 19 g of the expected product (yield=99%). |
Here is a chemical reaction formula: Reactants are:m4:C(C1=CC=CC=C1)Br;m1_m2_m3_m7_m5:COC1=C2C=C(NC2=CC=C1)C;m1_m2_m3_m7_m5:[H-].[Na+];m1_m2_m3_m7_m5:CCCCCC, Reagents are:m1_m2_m3_m7_m5:CN(C)C=O;m1_m2_m3_m7_m5:CN(C)C=O;m6:O, and Products are 0:COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Methoxy-2-methyl-1H-indole (1 g, 6.2 mmol) was added to 248 mg (6.2 mmol) of 60% sodium hydride/mineral oil (washed with hexane before adding DMF) in 15 mL of DMF and after stirring for 0.5 hour, 0.74 mL (6.2 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for 18 hours, diluted with water and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried (MgSO4) and after concentrating at reduced pressure, the residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 1.3 g (84% yield) of 4-methoxy-2-methyl-1-(phenylmethyl)-1H-indole, melting at 96°-116° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C;m1_m2_m3:B(Br)(Br)Br.C(Cl)Cl, Reagents are:m1_m2_m3:C(Cl)Cl, and Products are 0:OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 1.25 g (5 mmol) of 4-methoxy-2-methyl-1-(phenylmethyl)-1H-indole and 20 mL of 1M BBr3 /CH2Cl2 in 50 mL of methylene chloride was stirred at room temperature for 5 hours and concentrated at reduced pressure. The residue was dissolved in ethyl acetate, washed with brine and dried (MgSO4). After concentrating at reduced pressure, the residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 577 mg (49% yield) of 4-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole, 125°-127° C. |
Here is a chemical reaction formula: Reactants are:m3:BrCC(=O)OC;m1_m2_m4:OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C;m1_m2_m4:[H-].[Na+], Reagents are:m1_m2_m4:CN(C)C=O;m5:O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Hydroxy-2-methyl-1-(phenylmethyl)-1H-indole (530 mg, 2.2 mmol) was added to 88 mg (2.2 mmol) of 60% NaH/mineral oil in 20 mL of DMF and the mixture stirred for 0.67 hours. Then, 0.21 mL (2.2 mmol) of methyl bromoacetate was added and stirring maintained for 17 hours. The mixture was diluted with water and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried (MgSO4), and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 597 mg (88% yield) of [[2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester, 140°-143° C. |
Here is a chemical reaction formula: Reactants are:m2_m3_m5:OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C;m2_m3_m5:[H-].[Na+];m4:BrC(C(=O)OC)C, Reagents are:m2_m3_m5:CN(C)C=O, and Products are 0:COC(C(C)OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O;0:CCOC(=O)C.CCCCCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Hydroxy-2-methyl-1-(phenylmethyl)-1H-indole (483 mg, 2.0 mmol) was reacted with 82 mg (2.0 mmol) of 60% NaH/mineral oil in 20 mL of DMF and then with 0.22 mL (2.0 mmol) of dl-methyl 2-bromopropionate as described in Example 1, Part E to give after chromatography on silica gel eluting with 20% EtOAc/hexane 480 mg (74% yield) of dl-2-[[2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid methyl ester. |
Here is a chemical reaction formula: Reactants are:m3:N;m1_m2:C(C(=O)Cl)(=O)Cl;m1_m2:COC(C(C)OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O, Reagents are:m4:CCOC(=O)C, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)OC)C)CC1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Oxalyl chloride (0.16 mL, 1.9 mmol) was reacted with 480 mg (1.5 mmol) of dl-2-[[2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid methyl ester and then reacted with anhydrous ammonia as in Example 1, Part F and the reaction product was dissolved in EtOAc, washed with water, dried (MgSO4) and concentrated. The residue was chromatographed on silica gel (eluted with EtOAc) to give 531 mg (90% yield) of dl-2-[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid, methyl ester, melting at approximately 175° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(C(C)OC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)C)C(C(=O)N)=O)=O;m1_m2_m3:[OH-].[Na+], Reagents are:m1_m2_m3:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)O)C)CC1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 521 mg (1.3 mmol) of dl-2-[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid methyl ester and 10 mL of 1N NaOH in 30 mL of methanol was heated to maintain reflux for 0.17 hours, cooled to room temperature and stirred for 0.5 hour. The mixture was concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, made acidic to pH 2-3 with 1N HCl and extracted with EtOAc. The EtOAc solution was concentrated at reduced pressure and the residue stirred with a EtOAc-ether mixture. The insoluble material was filtered to give 246 mg (50% yield) of dl-2-[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid, mp, 201°-204° C. |
Here is a chemical reaction formula: Reactants are:m3_m2:ClCl;m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1, Reagents are:m3_m2:B(Br)(Br)Br, and Products are 0:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.6 g (4.9 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 20 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 841 mg (55% yield) of 1-([1,1'-biPhenyl]-2-ylmethyl)-4-hydroxy-2-methyl-1H-indole. |
Here is a chemical reaction formula: Reactants are:m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1;m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+], Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-([1,1'-Biphenyl]-2-ylmethyl)-4-hydroxy-2-methyl-1H-indole (767 mg, 2.45 mmol) was alkylated by treating with 0.23 mL (2.45 mmol) of methyl bromoacetate and 98 mg (2.45 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 730 mg (77% yield) of [[1-([1,1'-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 99°-101° C. |
Here is a chemical reaction formula: Reactants are:m1_m3_m4:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)C(C(=O)N)=O)=O;m0_m2:[Na], Reagents are:m1_m3_m4:[OH-].[Na+];m1_m3_m4:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 648 mg (1.4 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 10 mL of 1N NaOH and 20 mL of MeOH was heated to maintain reflux for 1 hour, cooled to room temperature and stirred 0.5 hour. The mixture was concentrated, the residue stirred with a mixture of EtOAc/water and the solid material that did not dissolve was filtered and dried to give 227 mg (35% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid, sodium salt, mp, >265° C. |
Here is a chemical reaction formula: Reactants are:m2_m3:B(Br)(Br)Br;m2_m3:ClCl;m1:C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1, Reagents are:, and Products are 0:C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.25 g (3.8 mmol) of 1-([1,1'-biphenyl]-3-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 15.2 mL of 1M BBr3 /CH2 Cl2 to give 1.03 g (87% yield) of crude 1-([1,1'-biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole. |
Here is a chemical reaction formula: Reactants are:m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+];m1:C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1, Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC=1C=C(C=CC1)C1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-([1,1'-Biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole (1.03 g, 3.3 mmol) was alkylated by treating with 0.31 mL (3.3 mmol) of methyl bromoacetate and 132 mg (3.3 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 1.0 g (79% yield) of [[1-([1,1'-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 99°-102° C. |
Here is a chemical reaction formula: Reactants are:m2_m3:B(Br)(Br)Br;m2_m3:ClCl;m1:C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1, Reagents are:, and Products are 0:C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.3 g (4.0 mmol) of 1-([1,1'-biphenyl]-4-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 16 mL of 1M BBr3 /CH2 Cl2 to give 970 mg (77% yield) of crude 1-([1,1'-biphenyl]-4-ylmethyl)-4-hydroxy-2-methyl-1H-indole. |
Here is a chemical reaction formula: Reactants are:m1:C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1;m2:[H-].[Na+];m3:BrCC(=O)OC, Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 1-([1,1'-biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole (970 mg, 3.1 mmol) was treated with 124 mg (3.1 mmol) of 60% NaH/mineral oil and then 0.29 mL (3.1 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 747 mg (63% yield) of [[1-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 164°-167° C. |
Here is a chemical reaction formula: Reactants are:m1:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)C(C(=O)N)=O)=O;m2_m0_m3:CO;m2_m0_m3:[Na], Reagents are:m4:[OH-].[Na+], and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 2, Part E, 803 mg (1.8 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester was hydrolyzed in 10 mL of 1N NaOH and 20 mL of MeOH to give 614 mg (74% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid, sodium salt, mp, >265° C. |
Here is a chemical reaction formula: Reactants are:m1:ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)OC)C;m2:B(Br)(Br)Br.C(Cl)Cl, Reagents are:, and Products are 0:ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.08 g (3.38 mmol) of 1-[(2,6 dichlorophenyl)methyl]-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 13.5 mL of 1M BBr3 /CH2Cl2 to give 862 mg (83% yield) of 1-[(2,6-dichlorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole, after chromatography on silica gel (eluted with 20% EtOAc/hexane). |
Here is a chemical reaction formula: Reactants are:m3:BrCC(=O)OC;m1:ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C;m2:[H-].[Na+], Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 1-[(2,6-dichlorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole (862 mg, 2.8 mmol) was treated with 112 mg (2.8 mmol) of 60% NaH/mineral oil and then 0.27 mL (2.8 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 411 mg (39% yield) of [[1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester,-mp, 168°-169° C. |
Here is a chemical reaction formula: Reactants are:m4_m5:C(C)(=O)OCC;m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)C(C(=O)N)=O)=O;m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, Reagents are:m4_m5:O, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1Cl)Cl)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 420 mg (0.94 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 5 mL of 1N NaOH and 15 mL of MeOH was heated to maintain reflux for 0.17 hours, cooled to room temperature and stirred 0.5 hours. Ethyl acetate and water was added, the aqueous layer separated, made acidic to pH 2-3 with 1N HCl, and the mixture extracted with ethyl acetate two times. The part that was not soluble was filtered. The filtrate was dried (MgSO4) and concentrated. The remaining solid was washed with a small volume of ether/methylene chloride and the insoluble material filtered and combined with the filtered material above to give 351 mg (86% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid, mp, 236°-239° C. |
Here is a chemical reaction formula: Reactants are:m4:FC1=CC=C(CCl)C=C1;m1_m2_m3_m7_m5:COC1=C2C=C(NC2=CC=C1)C;m1_m2_m3_m7_m5:[H-].[Na+];m1_m2_m3_m7_m5:CCCCCC, Reagents are:m1_m2_m3_m7_m5:CN(C)C=O;m1_m2_m3_m7_m5:CN(C)C=O;m6:O, and Products are 0:FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Methoxy-2-methyl-1H-indole (805 mg, 5 mmol) was added to a mixture of 200 mg (5 mmol) of 60% sodium hydride/mineral oil (washed with hexane before adding DMF) in 10 mL of DMF and after stirring for 0.5 hours, 0.6 mL (5 mmol) of 4-fluorobenzyl chloride was added. The mixture was stirred at room temperature for 18 hours, diluted with water-and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried (MgSO4) and after concentrating at reduced pressure, the residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 1.1 g (84% yield) of 1-[(4-fluorophenyl)methyl]-4-methoxy-2-methyl-1H-indole, melting at 104°-108° C. |
Here is a chemical reaction formula: Reactants are:m1:FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C;m2:B(Br)(Br)Br.C(Cl)Cl, Reagents are:, and Products are 0:FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.1 g (4.1 mmol) of 1-[(4-fluorophenyl)methyl]-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 16.4 mL of 1M BBr3 /CH2Cl2 to give 881 mg (84% yield) of crude 1-[(4-fluorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole. |
Here is a chemical reaction formula: Reactants are:m2:[H-].[Na+];m3:BrCC(=O)OC;m1:FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C, Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 1-[(4-fluorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole (881 mg, 3.45 mmol) was treated with 138 mg (3.45 mmol) of 60% NaH/mineral oil and then 0.33 mL (3.45 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 914 mg (81% yield) of [[1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, mp, 92°-98° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)C(C(=O)N)=O)=O;m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO;m4_m5:C(C)(=O)OCC, Reagents are:m4_m5:O, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)F)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 767 mg (1.9 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 10 mL of 1N NaOH and 30 mL of MeOH was heated to maintain reflux for 0.67 hours, cooled to room temperature and stirred 1 hour. Ethyl acetate and water were added and the aqueous layer separated, made acidic to pH 2-3 with 1N HCl and the mixture extracted with ethyl acetate two times. The combined ethyl acetate extracts were dried (MgSO4) and concentrated. The remaining solid was washed with a small volume of ethyl acetate to give 593 mg (81% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid, mp, 244°-247° C. |
Here is a chemical reaction formula: Reactants are:m3:ClCC1=CC=CC2=CC=CC=C12;m1_m4:COC1=C2C=C(NC2=CC=C1)C;m2:[H-].[Na+], Reagents are:m1_m4:CN(C)C=O;m5:O, and Products are 0:COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Methoxy-2-methyl-1H-indole (644 mg, 4 mmol) was dissolved in 10 mL of DMF and 160 mg (4 mmol) of 60% NaH/mineral oil was added. After 0.67 hours, 707 mg (4 mmol) of 1-(chloromethyl)naphthalene was added. After 5 hours, the mixture was diluted with water and extracted twice with ethyl acetate. The combined ethyl acetate was washed with brine, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 1.17 g (97% yield) of 4-methoxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole. |
Here is a chemical reaction formula: Reactants are:m2:B(Br)(Br)Br.C(Cl)Cl;m1:COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C, Reagents are:m3_m0:CCOC(=O)C.CCCCCC, and Products are 0:OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.17 g (3.9 mmol) of 4-methoxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole was O-demethylated by treating it with 15.6 mL of 1M BBr3 /CH2Cl2 to give a material that was chromatographed on silica gel (eluted with 20% EtOAc/hexane then 50% EtOAc/hexane) to give 796 mg (71% yield) of 4-hydroxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole. |
Here is a chemical reaction formula: Reactants are:m2:[H-].[Na+];m3:BrCC(=O)OC;m1:OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C, Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 4-hydroxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole (796 mg, 2.8 mmol) was treated with 112 mg (2.8 mmol) of 60% NaH/mineral oil and then 0.27 mL (0.27 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane to give 450 mg (45% yield) of [[2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid methyl ester, 167°-171° C. |
Here is a chemical reaction formula: Reactants are:m3_m6:CON(C(CC)=O)C;m1_m4_m2_m5:C(C)(CC)[Li];m1_m4_m2_m5:C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C, Reagents are:m3_m6:C1CCOC1;m1_m4_m2_m5:C1CCCCC1;m1_m4_m2_m5:C1CCOC1, and Products are 0:C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)CC(CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 140 mL (0.18 mol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (21.3 g, 0.09 mol) in 250 mL of THF keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to 0° C. and then the bath replaced. After the temperature had cooled to -60° C., 18.5 g (0.18 mol) of N-methoxy-N-methylpropanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 5 minutes, the cooling bath removed and stirred an additional 18 hours. It was then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated at reduced pressure to give 25.5 g of a crude of 1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone. This material was dissolved in 250 mL of methylene chloride and 50 mL of trifluoroacetic acid and stirred for a total of 17 hours. The mixture was concentrated at reduced pressure and ethyl acetate and water added to the remaining oil. The ethyl acetate was separated, washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed three times on silica eluting with 20% EtOAc/hexane to give 13.9 g of 2-ethyl-4-methoxy-1H-indole. |
Here is a chemical reaction formula: Reactants are:m3:C(C1=CC=CC=C1)Br;m2:[H-].[Na+];m1_m4:C(C)C=1NC2=CC=CC(=C2C1)OC, Reagents are:m5:O;m1_m4:CN(C)C=O, and Products are 0:C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Ethyl-4-methoxy-1H-indole (4.2 g, 24 mmol) was dissolved in 30 mL of DMF and 960 mg (24 mmol) of 60% NaH/mineral oil was added. After 1.5 hours, 2.9 mL (24 mmol) of benzyl bromide was added. After 4 hours, the mixture was diluted with water and extracted twice with ethyl acetate. The combined ethyl acetate was washed with brine, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 3.1 g (49% yield) of 2-ethyl-4-methoxy-1-(phenylmethyl)-1H-indole. |
Here is a chemical reaction formula: Reactants are:m2:B(Br)(Br)Br.C(Cl)Cl;m1:C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1, Reagents are:, and Products are 0:C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 3.1 g 11.7 mmol of 2ethyl-4-methoxy-1-(phenylmethyl)-1H-indole was O-demethylated by treating it with 48.6 mL of 1M BBr3 /CH2Cl2 to give a material that was chromatographed on silica gel (eluted with 20% EtOAc/hexane) to give 1.58 g (54% yield) of 2-ethyl-4-hydroxy-1-(phenylmethyl)-1H-indole, mp, 86°-90° C. |
Here is a chemical reaction formula: Reactants are:m3:BrCC(=O)OC;m1:C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1;m2:[H-].[Na+], Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 2-ethyl-4-hydroxy-1-(phenylmethyl)-1H-indole (1.56 g, 6.2 mmol) was treated with 248 mg (6.2 mmol) of 60% NaH/mineral oil and then 0.6 mL (6.2 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 1.37 g (69% yield) of [[2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester, 89°-92° C. |
Here is a chemical reaction formula: Reactants are:m1:ClC=1C=C(C=CC1)CN1C(=CC2=C(C=CC=C12)O)CC;m3:BrCC(=O)OC;m2:[H-].[Na+], Reagents are:, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 1, Part E, 1-[(3-chlorophenyl)methyl]-2-ethyl-4-hydroxy-1H-indole (512 mg, 1.8 mmol) was treated with 72 mg (1.8 mmol) of 60% NaH/mineral oil and then 0.17 mL (1.8 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 418 mg (65% yield) of [[1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester, mp, 85°-90° C. |
Here is a chemical reaction formula: Reactants are:m2_m0_m3:CO;m2_m0_m3:[Na];m1:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)C(C(=O)N)=O)=O, Reagents are:m4:[OH-].[Na+], and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC(=CC=C1)Cl)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 2, Part E, 418 mg (1 mmol) of [[3-(2-amino-1,2-dioxoethyl)1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester was hydrolyzed in 5 mL of 1N NaOH and 15 mL of MeOH to give 268 mg (61% yield) of [[3-(2-amino-1,2-dioxoethyl)1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol -4-yl]oxy]acetic acid, sodium salt, mp, >265° C. |
Here is a chemical reaction formula: Reactants are:m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)CC)C1=CC=CC=C1;m3_m2:ClCl, Reagents are:m3_m2:B(Br)(Br)Br, and Products are 0:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 911 mg (2.6 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-4-methoxy-1H-indole was O-demethylated by treating it with 10 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 590 mg (69% yield) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-4-hydroxy-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1;m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+], Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-([1,1'-Biphenyl]-2-ylmethyl)-2-ethyl-4-hydroxy-1H-indole (911 mg, 2.8 mmol) was alkylated by treating with 0.26 mL (2.8 mmol) of methyl bromoacetate and 111 mg (2.8 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 655 mg (59% yield) of [[1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)C(C(=O)N)=O)=O, Reagents are:m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 600 mg (1.3 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 8 mL of 1N NaOH and 20 mL of MeOH was heated to maintain reflux for 0.67 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, made acidic with 1N HCl and extracted with EtOAc. The EtOAc solution was dried (MgSO4) and evaporated and the residue crystallized from MeOH to give 352 mg (59% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid, mp, 211°-214° C. |
Here is a chemical reaction formula: Reactants are:m3:C1CCOC1;m4_m5:CON(C(CCC)=O)C;m4_m5:C1CCOC1;m1_m6_m2:C(C)(CC)[Li];m1_m6_m2:C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C, Reagents are:m1_m6_m2:C1CCCCC1, and Products are 0:C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)CC(CCC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 50 mL (65 mmol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (7.7 g, 32.5 mmol) in 100 mL. of THF keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -10° C. and then the bath replaced. After the temperature had cooled to -60° C., 4.3 g (32.5 mmol) of N-methoxy-N-methylbutanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 1 hour, the cooling bath removed and stirred an additional 22 hours. It was then poured into a mixture of 200 mL of ether and 200 mL of 0.5N HCl. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated at reduced pressure to give 9.9 g of crude 1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-pentanone. This material was dissolved in 100 mL of methylene chloride and 20 mL of trifluoroacetic acid and stirred for a total of 23 hours. The mixture was washed with water, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 2.19 g of 4-methoxy-2-propyl-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m2_m3:B(Br)(Br)Br;m2_m3:ClCl;m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)CCC)C1=CC=CC=C1, Reagents are:, and Products are 0:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.16 g (3.27 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-4-methoxy-2-propyl-1H-indole was O-demethylated by treating it with 13 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 794 mg (71% yield) of 1-([1,1'-biphenyl]-2-ylmethyl)-4-hydroxy-2-propyl-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+];m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1, Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-([1,1'-Biphenyl]-2-ylmethyl)-4-hydroxy-2-propyl-1H-indole (794 mg, 2.8 mmol) was alkylated by treating with 0.22 mL (2.3 mmol) of methyl bromoacetate and 93 mg (2.3 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 533 mg (56% yield) of [[1-([1,1'-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid methyl ester. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)C(C(=O)N)=O)=O, Reagents are:m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 440 mg (0.9 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 5 mL of 1N NaOH and 15 mL of MeOH was stirred for 0.75 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, made acidic with 1N HCl to pH 2-3 and extracted with EtOAc. The EtOAc solution was dried (MgSO4) and evaporated to give 374 mg (88% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid. |
Here is a chemical reaction formula: Reactants are:m0_m3:C1(CC1)C(=O)CC1=C(C=CC=C1OC)NC(=O)OC(C)(C)C;m2_m4:C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C;m2_m4:C1CCOC1;m1:C(C)(CC)[Li], Reagents are:m5:C1CCCCC1, and Products are 0:CON(C(=O)C1CC1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Using the procedure described in Example 9, Part A, 100 mL (130 mmol) of 1.3M sec-butyl lithium in cyclohexane was reacted with N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (15.4 g, 65 mmol) in 100 mL of THF and then with 8.4 g (65 mmol) of N-methoxy-N-methylcyclopropylcarboxamide to give crude [2-(tert-butoxycarbonylamino)-6-methoxyphenyl]methyl cyclopropyl ketone. This material on treatment with 20 mL of trifluoroacetic acid in 300 mL of methylene chloride for 6 hours gave a material that was chromatographed on silica gel. Eluting with a gradient, toluene→5% EtOAc/toluene, there was obtained 6.4 g (52% yield) of 2-cyclopropyl-4-methoxy-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m1:C1(CC1)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1;m2:B(Br)(Br)Br.C(Cl)Cl, Reagents are:, and Products are 0:C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 630 g (2.3 mmol) of 2-cyclopropyl-4-methoxy-1-(phenylmethyl)-1H-indole was O-demethylated by treating it with 9 mL of 1M BBr3 /CH2Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 316 mg (52% yield) of 2-cyclopropyl-4-hydroxy-1-(phenylmethyl)-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+];m1:C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1, Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Cyclopropyl-4-hydroxy-1-(phenylmethyl)-1H-indole (316 mg, 1.2 mmol) was alkylated by treating with 0.11 mL (1.2 mmol) of methyl bromoacetate and 48 mg (1.2 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to give 253 mg (63% yield) of [[2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)C(C(=O)N)=O)=O, Reagents are:m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=CC=C1)C1CC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 220 mg (0.54 mmol) of [[3-(2-amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester in 5 mL of 1N NaOH and 15 mL of MeOH was heated to maintain reflux for 0.67 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, made acidic with 1N HCl to pH 2-3 and EtOAc added. A precipitate formed and was separated to give 169 mg (80% yield) of [[3-(2-amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid, mp, 246°-249° C. |
Here is a chemical reaction formula: Reactants are:m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C1CC1)C1=CC=CC=C1;m2_m3:B(Br)(Br)Br;m2_m3:ClCl, Reagents are:, and Products are 0:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method used in Example 1, Part D, 1.25 g (3.7 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-4-methoxyl-1H-indole was O-demethylated by treating it with 15 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 367 mg (29% yield) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-4-hydroxy-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m1:C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1;m2_m3_m4:BrCC(=O)OC;m2_m3_m4:[H-].[Na+], Reagents are:m2_m3_m4:CN(C)C=O, and Products are 0:COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-([1,1'-Biphenyl]-2-ylmethyl)-2-cyclopropyl-4-hydroxy-1H-indole (367 mg, 1.1 mmol) was alkylated by treating with 0.1 mL (1.1 mmol) of methyl bromoacetate and 43 mg (1.1 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane to give 265 mg (59% yield) of [[1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid methyl ester. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)C(C(=O)N)=O)=O, Reagents are:m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 175 mg (0.36 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]0xy]acetic acid methyl ester in 4 mL of 1N NaOH and 10 mL of MeOH was stirred for 0.5 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, made acidic with 1N HCl to pH 2-3 and extracted with EtOAc. The EtOAc solution was dried (MgSO4), evaporated and the residue stirred with EtOAc/ether. The insoluble material was filtered to give 105 mg (62% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid, mp, 172°-174° C. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:C(C)(CC)[Li].C1CCCCC1;m1_m2_m4:C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)C;m3_m5:CON(C(CC)=O)C, Reagents are:m1_m2_m4:C1CCOC1;m3_m5:C1CCOC1, and Products are 0:C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 1.3M sec-butyl lithium/cyclohexane (81 mL, 0.105 mol) was added slowly to 11.85 g (0.05 mol) of N-tert-butoxycarbonyl-4-methoxy-2-methylaniline in 80 mL of THF while keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -20° C. and then the bath was replaced. After the temperature had cooled to -60° C., 6.1 g (0.052 mol) of N-methoxy-N-methylpropanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 1 hour, the cooling bath removed and stirred an additional 1 hour. It was then poured into a mixture of 200 mL of ether and 200 mL of 1N HCl. The organic layer was separated, washed with water, dried over Na2 SO4 and concentrated at reduced pressure to give 10.9 g (74% yield) of 1-(2-(tert-butoxycarbonylamino)-5-methoxyphenyl]-2-butanone, melting at 80°-81° C., after chromatography on silica eluting with 5% EtOAc/toluene. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O, Reagents are:m1_m2_m3:C(Cl)Cl;m1_m2_m3:FC(C(=O)O)(F)F, and Products are 0:C(C)C=1NC2=CC=C(C=C2C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-[2-(tert-Butoxycarbonylamino)-5-methoxyphenyl]-2-butanone (7.33 g, 0.025 mol) in 120 mL of CH2Cl2 and 20 mL of trifluoroacetic acid was stirred for 20 hours, washed with water, NaHCO3 solution and the product chromatographed on silica (eluted with 20% EtOAc/hexane) to give 2.54 g (58% yield) of 2-ethyl-5-methoxy-1H-indole as a white solid, mp 49°-50° C. |
Here is a chemical reaction formula: Reactants are:m1_m5:C(C)C=1NC2=CC=C(C=C2C1)OC;m2_m3:C1CCOC1;m2_m3:[H-].[Na+];m4:C(C1=CC=CC=C1)Br, Reagents are:m6:O;m1_m5:CN(C)C=O, and Products are 0:C(C)C=1N(C2=CC=C(C=C2C1)OC)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Ethyl-5-methoxy-1H-indole (5.6 g, 21.5 mmol) was dissolved in 150 mL of DMF and 20 mL of THF and 1.0 g (25 mmol) of 60% sodium hydride was added. After stirring for 0.17 hours, 3.0 mL (25 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for 10 hours, diluted with water and extracted with ethyl acetate. The ethyl acetate solution was washed with water, saturated NaCl solution, and dried (Na2 SO4). The EtOAc was evaporated and the residue was chromatographed on silica gel eluting with a gradient, 5% EtOAc/hexane→15% EtOAc/hexane to give 4.6 g (82% yield) of 2-ethyl-5-methoxy-1-(phenylmethyl)-1H-indole. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)OC(CCCOC=1C=C2C(=C(N(C2=CC1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O, Reagents are:m1_m2_m3:C(Cl)Cl;m1_m2_m3:FC(C(=O)O)(F)F, and Products are 0:NC(C(=O)C1=C(N(C2=CC=C(C=C12)OCCCC(=O)O)CC1=CC=CC=C1)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 450 mg (0.97 mmol) of 4-[[3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid tert-butyl ester in 75 mL of methylene chloride and 1 mL of trifluoroacetic acid was stirred-at room temperature for 2.25 hours and concentrated at reduced pressure. The residue was chromatographed on silica gel and eluted with EtOAc to give 250 mg (63% yield) of 4-[[3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid, mp 173°-175° C. |
Here is a chemical reaction formula: Reactants are:m3:C(C1=CC=CC=C1)Br;m1_m2:COC=1C=C2C=CNC2=CC1;m1_m2:[H-].[Na+];m4:B(Br)(Br)Br.C(Cl)Cl, Reagents are:m5:C(Cl)Cl, and Products are 0:OC=1C=C2C=CN(C2=CC1)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 5-Methoxy-1H-indole (5.6 g, 21.5 mmol) was reacted with 1.0 g (25 mmol) of 60% sodium hydride and then 3.0 mL (25 mmol) of benzyl bromide by the method described in Example 12, Part D to give crude 5-methoxy-1-(phenylmethyl)-1H-indole. This material was dissolved in 250 mL of methylene chloride, cooled to -5° C., 50 mL of 1M BBr3 /CH2Cl2 added, the cooling bath removed and the mixture stirred for 1.75 hours. Ice water was added and the mixture stirred. The organic layer was separated, washed with saturated NaCl, dried (Na2 SO4), and concentrated at reduced pressure. The residue was chromatographed on silica gel and eluted with 20% ether/hexane→ether to give 870 mg (19% overall yield) of crude 5-hydroxy-1-(phenylmethyl)-1H-indole. |
Here is a chemical reaction formula: Reactants are:m4:C(C1=CC=CC=C1)Br;m1_m2_m3_m7_m5:C(C)C=1NC2=CC=CC(=C2C1)[N+](=O)[O-];m1_m2_m3_m7_m5:[H-].[Na+];m1_m2_m3_m7_m5:CCCCCC, Reagents are:m6:O;m1_m2_m3_m7_m5:CN(C)C=O;m1_m2_m3_m7_m5:CN(C)C=O, and Products are 0:C1(=CC=CC=C1)CN1C(=CC2=C(C=CC=C12)[N+](=O)[O-])CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Ethyl-4-nitro-1H-indole (4.75 g, 25 mmol) was added to a mixture of 1.0 g (25 mmol) of 60% NaH/mineral oil (washed with hexane before adding DMF) in 40 ml DMF. After 45 minutes, 3.0 ml (25 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for four hours, diluted with water, and extracted with EtOAc. The EtOAc solution was washed with brine, dried over MgSO4, and evaporated in vacuo. The residue was chromatographed on silica gel eluting with 20% EtOAc/Hexane to give 6.36 g (91%) of 1-Phenylmethyl-2-ethyl-4-nitro-1H-indole as an oil. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrCC(=O)OC;m1_m2_m3:NC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O, Reagents are:m4:O;m1_m2_m3:CN(C)C=O, and Products are 0:COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Methyl bromoacetate (0.07 ml, 0.78 mmol) was added to 250 mg (0.78 mmol) of 4-Amino-2-Ethyl-α-oxo-1-(phenylmethyl)-1H-indole-3-Acetamide in 4 ml of DMF, stirred at 60° C. for 0.5 hour, and then at room temperature for 20 hours. The mixture was diluted with water and extracted with EtOAc. The EtOAC solution was washed with brine, dried over MgSO4, and evaporated in vacuo. The residue was chromatographed over silica gel eluting with Hexane/50 to 100% EtOAc to give 196 mg (64%) of [[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]amino]acetic acid methyl ester melting at 188°-193° C. |
Here is a chemical reaction formula: Reactants are:m5_m4:Cl;m1_m2_m3:COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O;m1_m2_m3:[OH-].[Na+];m1_m2_m3:CO, Reagents are:m5_m4:CCOC(=O)C, and Products are 0:NC(C(=O)C1=C(N(C2=CC=CC(=C12)NCC(=O)O)CC1=CC=CC=C1)CC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 190 mg (0.48 mmol) of [[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]amino]acetic acid methyl ester, 5 ml of 1N NaOH, and 15 ml of MeOH was refluxed 0.33 hour, cooled, and stirred at room temperature for 1 hour. EtOAc and aqueous HCl were added and the EtOAc layer was washed with brine, dried over MgSO4, and evaporated in vacuo. The residue was crystallized from MeOH to give 96 mg (53%) of [[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]amino]acetic acid melting at 151°-157° C. |
Here is a chemical reaction formula: Reactants are:m1:NC1=NC(=CC(=N1)NC1=CC(=CC(=C1)C(C)=O)C(C)=O)C;m2:CI, Reagents are:m3:C(C)#N.O1CCCC1, and Products are 0:[I-].NC1=[N+](C(=CC(=N1)NC1=CC(=CC(=C1)C(C)=O)C(C)=O)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 2, FIG. 1A: A suspension of Compound No. 11 (2-amino-4-(3,5-diacetylphenyl)amino-6-methylpyrimidine) (0.284 g), was suspended in 1:1 acetonitrile-tetrahydrofuran was treated with methyl iodide (2 mL) and heated at 40°-45° C. under a reflux condenser for 18 hr. Cooling and filtration gave 0.35 g of 2-amino-4-(3,5-diacetylphenyl)amino-1,6-dimethylpyrimidinium iodide, mp 292° C. |
Here is a chemical reaction formula: Reactants are:m1_m4:C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O;m2_m3:C(#N)NC(=N)N;m2_m3:Cl, Reagents are:m1_m4:O, and Products are 0:Cl.C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC(=N)NC(=N)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 12. A suspension of 3,5-diacetylaniline (0.531 g) in water (8 mL) was treated with cyanoguanidine (0.285 g) and conc. HCl (0.25 mL) and heated at reflux. After 6 hr the mixture was cooled and concentrated and 0.248 g of off-white solid was filtered out and dried to give N-(3,5-diacetylphenyl)biguanide hydrochloride, mp 260°-70° C. (dec). |
Here is a chemical reaction formula: Reactants are:m2_m3:ClC1=NC(=NC(=N1)N)N;m2_m3:Cl;m1_m5:C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O;m4:Cl, Reagents are:m1_m5:O, and Products are 0:C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=NC(=NC(=N1)N)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 13: A suspension of 3,5-diacetylaniline (1.95 g) in water (10 mL) was treated with 2-chloro-4,6-diamino-1,3,5-triazine (1.455 g) and concentrated HCl (0.1 mL) and heated at reflux for 20 min. After cooling the hydrochloride of Compound No. 13 separated as a white powder. This was filtered out, dissolved in 60 mL of boiling aqueous 75% methanol and treated with triethylamine (1.5 mL). On cooling, off-white flakes separated. Filtration and drying gave 1.79 g of 2-(3,5-diacetylphenyl)amino-4,6-diamino-1,3,5-triazine, mp 271°-2° C. |
Here is a chemical reaction formula: Reactants are:m2:CI;m1:C(C)(=O)C=1C=C(C=CC1)NC1=NC(=NC(=C1)C)N, Reagents are:m3:CC(=O)C, and Products are 0:[I-].C(C)(=O)C=1C=C(C=CC1)NC1=NC(=[N+](C(=C1)C)C)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 14: 4-(3-acetylphenyl)amino-2-amino-6methylpyrimidine, Compound No. 15, (0.968 g) was suspended in acetone (5 mL) containing methyl iodide (2 mL) was heated at reflux for 48 hr. Filtration after cooling gave 0.657 g of 4-(3-acetylphenyl)amino-2-amino-1,6-dimethylpyrimidinium iodide as a white powder, mp 238°-40° C. |
Here is a chemical reaction formula: Reactants are:m3:Cl;m4:[OH-].[K+];m1_m2_m5:NC=1C=C(C=CC1)C(C)=O;m1_m2_m5:NC1=NC(=CC(=N1)Cl)C, Reagents are:m1_m2_m5:O, and Products are 0:C(C)(=O)C=1C=C(C=CC1)NC1=NC(=NC(=C1)C)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 15: A suspension of m-aminoacetophenone (2.7 g) and 2-amino-4-chloro-6-methylpyrimidine (2.87 g) in 40 mL water was treated with 1.7 mL concentrated HCl and heated at reflux for 1 hour. Addition of 40 mL 1N KOH gave a light buff solid, which was filtered out and dried to give 3.8 g 4-(3-acetylphenyl)amino-2-amino-6-methylpyrimidine, mp 196°-98° C. |
Here is a chemical reaction formula: Reactants are:m1_m5:C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O;m4:[OH-].[K+];m2_m3:ClC1=C2NC=NC2=NC=N1;m2_m3:Cl, Reagents are:m1_m5:O, and Products are 0:C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=C2NC=NC2=NC=N1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Compound No. 16: A suspension of 3,5-diacetylaniline (0.531 g) in water (10 mL) was treated with 6-chloropurine (0.464 g) and concentrated HCl (0.25 mL) and heated at reflux for 30 min. After cooling the mixture was treated with 6 mL of aqueous 1N KOH. The mixture was stirred for 10 min and the solid was filtered out, washed with water, and dried, to give 0.80 g of 6-[(3,5-diacetylphenyl)amino]purine, mp dec 340°-350° C. |
Here is a chemical reaction formula: Reactants are:m2:C(CC(=O)C)(=O)OCC;m3_m5:C(C1=CC=CC=C1)Br;m1_m4:[H-].[Na+], Reagents are:m6:C1CCOC1;m3_m5:C1CCOC1;m1_m4:CCCCCC, and Products are 0:C(C)OC(CC(=O)CCC1=CC=CC=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: NaH (13.8 g, 0.6 mole) was washed twice with hexane (2×50 ml) and suspended in 250 ml of freshly distilled THF. Next ethyl acetoacetate (75 ml, excess) was added dropwise carefully while the receiving flask was cooled at -10° C. After the addition was complete, it was stirred at -10° C. for 2 hours and at room temperature for 30 min. Benzylbromide (51.0 g, 0.3 mole) in THF was added dropwise at room temperature to the above solution. The reaction mixture was stirred overnight at room temperature. The reaction was terminated the next day by pouring into ice cold water, brought to neutral pH, and extracted with ether/ethylacetate. The combined ether/ethylacetate extracts were rinsed over brine and dried over Na2SO4. Removal of the solvent followed by careful vacuum distillation gave ethyl-benzylacetoacetate, bp 276° C. IR: (neat), cm-1 : 2900-3050, 1690-1760 (broad), 1655. NMR (CDCl3):δ:1.25 (t1 3H, CH2CH3); 2.25 (s, 3H, COCH3); 3.20 (d, 2H, benzylic CH2); 3.8 (t, 1H, COCHCO); 4.20 (q, 2H, OCH2CH3); 7.15-7.35 (m, 5H, Ar-H). |
Here is a chemical reaction formula: Reactants are:m1_m2:CC1=C(CC2=CC=CC=C12)C(=O)O;m1_m2:S(=O)(Cl)Cl, Reagents are:, and Products are 0:CC1=C(CC2=CC=CC=C12)C(=O)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1.0 g of 3-methylindene-2-carboxylic acid and 5 ml thionyl chloride were refluxed for 4 hours. Careful removal of the solvent by distillation under reduced pressure gave 3-methylindene-2-oyl chloride. The acid chloride dissolved in THF was dropped into a mixture of guanidine and sodium hydroxide at room temperature over a period of 10 min. and stirred for one hour. The reaction was terminated by work-up and the product was purified by column chromatography. |
Here is a chemical reaction formula: Reactants are:m1_m4:C1(CCC2=CC=CC=C12)=O;m2:C(CCC)[Li];m3:ClC(=O)OCC, Reagents are:m1_m4:C1CCOC1, and Products are 0:C(=O)(OCC)C1C(C2=CC=CC=C2C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-Indanone (1.5 g, 11.36 mmols) was dissolved in dry THF in a three neck flask equipped with nitrogen inlet, septum and a guard tube. The flask was cooled to -20° C. for 10 minutes. Then butyl lithium (11.37 ml, 12.48 mmols) was added dropwise through the septum using the syringe. The reaction mixture was allowed to stand at -20° C. for 45 minutes and then ethyl chloroformate (1.08 ml, 10 mmols) was added dropwise using a syringe. The reaction mixture was stirred at -20° C. for 30 minutes and slowly brought to room temperature in about one hour. The reaction was worked-up by evaporating the THF and the product was chromatographed to yield 2-carbethoxy-1-indanone. NMR: (CDCl3):δ:1.25 (t, 3H, OCH2CH3); 3.45 (d, 2H, benzylic CH2); 3.65 (t, 1H, COCHCO); 4.2 (q, 2H, OCH2CH3); 7.4-7.5 (m, 4H, Ar-H). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(=O)(OCC)C1C(C2=CC=CC=C2C1)=O, Reagents are:m1_m2_m3:CO;m1_m2_m3:[BH4-].[Na+], and Products are 0:C1C(=CC2=CC=CC=C12)C(=O)OCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-Carbethoxy-1-indanone was dissolved in dry methanol at room temperature, to which sodium borohydride was added in three lots while the reaction mixture was kept stirring. The reaction mixture was further stirred for 30 minutes, after which the solid was filtered and the filtrate was evaporated to dryness. The residue was dissolved in dry benzene, to which catalytic amount of p-toluenesulfonic acid was added and the reaction mixture was stirred for one hour. The p-toluenesulfonic acid was filtered off and the filtrate was concentrated to yield ethyl indene-2-carboxylate. The ethyl indene-2-carboxylate was dissolved in methanol and 1.0 equivalent of aqueous sodium hydroxide solution was added and the reaction mixture was kept stirring for overnight. The next day, the reaction was terminated by evaporating the methanol, followed by diluting the residue with water, brought to neutral pH and the precipitated indene-2-carboxylic acid was filtered. NMR: (CDCl3):δ:3.75 (s, 2H, benzylic CH2); 7.4-7.7 (m, 4H, Ar-H); 7.95 (s, 1H, olefinic H). |
Here is a chemical reaction formula: Reactants are:m2_m4:CN(C1=CC=C(C=C1)N=C=O)C;m1_m3:C(CCCC)NC[C@@H]1CC[C@H](CC1)CNCCCCC, Reagents are:m2_m4:C(C)#N;m1_m3:CCOCC, and Products are 0:CN(C1=CC=C(C=C1)NC(N(CCCCC)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N(C)C)CCCCC)=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Trans-1,4-bis[(normalpentylamino)methyl]cyclohexane, 0.56 g, was dissolved in 10 ml of ether. A solution of 0.81 g of 4-dimethylaminophenyl isocyanate in 20 ml of acetonitrile was added. The reaction mixture was stirred at room temperature for 10 hours. The solvent of the reaction mixture was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to provide 1.10 g (yield: 89%) of white crystals. |
Here is a chemical reaction formula: Reactants are:m2:[H][H];m1:C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)[N+](=O)[O-])C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)[N+](=O)[O-])C1CCCCC1, Reagents are:m4:[Pd];m3_m5:[C].[Pd];m3_m5:CN(C)C=O, and Products are 0:C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)N)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N)C1CCCCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 0.6 g quantity of 10% palladium carbon was added to 100 ml of a DMF solution containing 5.7 g of trans-1,4-bis[[1-cyclohexyl-3-(4-nitrophenyl)ureido]-metyl]cyclohexane synthesized in accordance with Example 2. Hydrogen was added at ordinal pressure and normal temperature for 15 hours. After completion of the reaction, palladium was separated by filtration and the reaction mixture was concentrated under reduced pressure. The reaction mixture was dissolved in chloroform and a 4N hydrochloric acid-dioxyane solution was added to provide 5.5 g (95%) of white crystals precipitated. |
Here is a chemical reaction formula: Reactants are:m1:[H-].[Na+];m4:O;m2_m3:CONC(OC)=O;m2_m3:C(C#C)Br, Reagents are:m5:O1CCCC1, and Products are 0:CON(C(OC)=O)CC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 0.43 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 1.0 g of methyl N-methoxycarbamate and 1.36 g of propargyl bromide were added to the suspension in this order while being cooled with ice. The mixture was heat-refluxed for 4 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography to obtain 0.8 g of methyl N-methoxy-N-propargylcarbamate. |
Here is a chemical reaction formula: Reactants are:m4:O;m1:[H-].[Na+];m2_m3:CONC(OC)=O;m2_m3:ClCOCC#C, Reagents are:m5:O1CCCC1, and Products are 0:CON(C(OC)=O)COCC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 0.37 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 0.8 g of methyl N-methoxycarbamate and 0.96 g of chloromethylpropargyl ether were added thereto in this order while being cooled with ice. The mixture was heat-refluxed for 1 hour. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography to obtain 1.0 g of methyl N-methoxy-N-propargyloxymethylcarbamate. |
Here is a chemical reaction formula: Reactants are:m2_m3:CONC(C1=CC=C(C=C1)Cl)=O;m2_m3:C(C#C)Br;m1:[H-].[Na+];m4:O, Reagents are:m5:O1CCCC1, and Products are 0:CON(C(C1=CC=C(C=C1)Cl)=O)CC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 0.22 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 1.0 g of N-methoxy-p-chlorobenzamide and 0.68 g of propargyl bromide were added thereto in this order while being cooled with ice. The mixture was heat-refluxed for 8 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography to obtain 0.44 g of N-methoxy-N-propargyl-p-chlorobenzamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:CONC(C1=C(C=C(C=C1)Cl)Cl)=O;m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+];m1_m2_m3_m4:C(C#C)Br;m1_m2_m3_m4:CN(C=O)C, Reagents are:m5:O, and Products are 0:CON=C(C1=C(C=C(C=C1)Cl)Cl)OCC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1.0 g of N-methoxy-2,4-dichlorobenzamide, 0.75 g of potassium carbonate and 0.65 g of propargyl bromide were added to 10 ml of N,N-dimethylformamide, and the mixture was stirred for 3 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography to obtain 0.35 g of propargyl N-methoxy-2,4-dichlorobenzimidate. |
Here is a chemical reaction formula: Reactants are:m1_m5:CONC(C1=CC=CC=C1)=O;m4:O;m2_m3:C([O-])([O-])=O.[K+].[K+];m2_m3:ClCOCC#C, Reagents are:m1_m5:C(C)#N, and Products are 0:CON(C(C1=CC=CC=C1)=O)COCC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 0.6 g of N-methoxybenzamide was dissolved in 10 ml of acetonitrile, and 0.55 g of potassium carbonate and 0.42 g of chloromethylpropargyl ether were added thereto in this order. The mixture was stirred at room temperature for 3 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography to obtain 0.8 g of N-methoxy-N-propargyloxymethylbenzamide. |
Here is a chemical reaction formula: Reactants are:m4:O;m2_m3:C([O-])([O-])=O.[K+].[K+];m2_m3:ClCOCC#C;m1_m5:CONS(=O)(=O)C1=CC=CC=C1, Reagents are:m1_m5:C(C)#N, and Products are 0:CON(S(=O)(=O)C1=CC=CC=C1)COCC#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 0.6 g of N-methoxybenzenesulfonamide was dissolved in 10 ml of acetonitrile, and 0.44 g of potassium carbonate and 0.34 g of chloromethylpropargyl ether were added thereto in this order. The mixture was stirred at room temperature for 4 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried, concentrated, and purified by silica gel column chromatography to obtain 0.7 g of N-methoxy-N-propargyloxymethylbenzenesulfonamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m5:C(C)OCC[O-].[Na+];m1_m2_m5:[Na];m3_m4:NC1=NC=C(C(=N1)N)C=O;m3_m4:ClC1=C(C(=CC=C1)Cl)CC#N, Reagents are:m1_m2_m5:C(C)OCCO, and Products are 0:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (Prepared by the method of U.S. Pat. No. 3,534,039). To a solution of sodium 2-ethoxyethoxide prepared from 0.14 g of sodium and 60 mL of 2-ethoxyethanol was added 2.07 g of 2,4-diamino-5-pyrimidinecarboxaldehyde and 2.79 g of 2,6-dichlorophenylacetonitrile. The mixture is heated at reflux for 4 hours, cooled, and the insoluble product washed with diethylether to give 2,7-diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine, mp 325-332° C. (MS). |
Here is a chemical reaction formula: Reactants are:m2:[H-].[Na+];m3:C(C)(C)(C)N=C=O;m1:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2)C)N, Reagents are:m4:CN(C=O)C, and Products are 0:C(C)(C)(C)NC(=O)NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2)C)NC(=O)NC(C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A suspension of 0.5 g of 2,7-diamino-6-o-tolyl-pyrido[2,3-d]pyrimidine, prepared as described above in Example 1, in 10 mL of dimethylformamide is reacted with 0.16 g of 60% sodium hydride and stirred at ambient temperature for 1.5 hours. To the suspension is added 0.49 mL of t-butylisocyanate and the mixture stirred overnight at ambient temperature. The reaction mixture is filtered to remove insoluble salts and the filtrate evaporated under reduced pressure. The residue is diluted with water, the insoluble crude product collected by filtration and dried in vacuo. Crystallization from a hexane:ethyl acetate: dichloromethane mixture (3:2:5 v/v/v) afforded the title compound, mp 209°-212° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m3:Cl;m1_m4_m2_m3:S(=O)(=O)([O-])OS(=O)(=O)[O-];m1_m4_m2_m3:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)N, Reagents are:m1_m4_m2_m3:O, and Products are 0:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 2 L of concentrated HCl and 1 L of water is added 300 g of the disulfate salt of 2,7-diamino-6-phenylpyrido[2,3-d]pyrimidine and the resulting mixture refluxed with stirring overnight. The reaction mixture is cooled in an ice bath, filtered, and the insoluble product washed with water, followed by ethanol to give 149 g of the title compound 2-amino-6-phenyl-pyrido[2,3-d]pyrimidin-7-ol, mp 390°-395° C. (darkens slowly above 350° C.). |
Here is a chemical reaction formula: Reactants are:m1:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)O;m3:S(=O)(Cl)Cl;m2_m4:ClCCl, Reagents are:m2_m4:CN(C=O)C, and Products are 0:C(CCC)NC=1C(=CC2=C(N=C(N=C2)N)N1)C1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 23.8 g of 2-amino-6-phenyl-pyrido-[2,3-d]pyrimidin-7-ol prepared above in Example 8, 250 mL of dichloromethane, and 77.5 mL of dimethylformamide was added dropwise with cooling 36 mL of thionyl chloride keeping the temperature below 15° C. Following complete addition, the suspension was heated to reflux with stirring for 5 hours. The solvents were removed in vacuo maintaining the temperature below 60° C. The resulting solid was added with cooling to 250 mL of n-butylamine and the suspension refluxed for 6 hours with stirring. The reaction mixture was allowed to cool to room temperature, filtered, and the volatile components of the filtrate removed on a rotary evaporator in vacuo. The viscous oil was partitioned between diethyl ether and water, the layers were separated, and the ethereal layer was washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated. The residue was partitioned between diethyl ether and dilute 1N HCl. The aqueous layer was washed three times with diethylether and made alkaline to pH 12 by addition of sodium hydroxide. The solid product was collected by filtration and dried in vacuo to afford 6.5 g of the title compound N7 -butyl-6-phenyl-pyrido[2,3-d]pyrimidine-2,7-diamine, mp 174°-181° C. dec. |
Here is a chemical reaction formula: Reactants are:m3:S(=O)(Cl)Cl;m1_m2_m4:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)O;m1_m2_m4:ClCCl;m1_m2_m4:CN(C=O)C, Reagents are:, and Products are 0:ClC=1C(=CC2=C(N=C(N=C2)N=CN(C)C)N1)C1=CC=C(C=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 67.0 g of 2-amino-6-(4-methoxy-phenyl)-pyrido[2,3-d]pyrimidin-7-ol from Example 10, 1 L of dichloromethane, and 155 mL of dimethylformamide was added dropwise with cooling 72 mL of thionyl chloride keeping the temperature below 15° C. The suspension was heated to reflux with stirring for 6 hours. The reaction mixture was filtered and the filtrate evaporated in vacuo maintaining the temperature below 60° C. The resulting residue was dissolved in ice water and aqueous sodium hydroxide added with ice. The product was taken up in chloroform, washed with water, dried over anhydrous potassium carbonate, and evaporated. The residue was slurried with acetonitrile and the insoluble product collected by filtration to afford 31 g of the title compound N'-(7-chloro-6-(4-methoxyphenyl)-pyrido[2,3-d]pyrimidin-2-yl)-N,N-dimethyl-formamidine. The product was used in the next step without further purification. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC=1C(=CC2=C(N=C(N=C2)N=CN(C)C)N1)C1=CC=C(C=C1)OC, Reagents are:m1_m2:C(C)O, and Products are 0:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 10 g of N'-(7-chloro-6-(4-methoxy-phenyl)-pyrido[2,3-d]pyrimidin-2-yl)-N,N-dimethyl-formamidine from Example 11 and 500 mL of 95% ethanol was refluxed for 3 hours. The solution was concentrated in vacuo and the precipitate collected by filtration. Crystallization from ethanol afforded 2.7 g of the title compound 2-amino-7-chloro-6-(4-methoxyphenyl)-pyrido[2,3-d]pyrimidine, mp 275°-280° C. dec. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)Cl;m1_m2_m3:CN, Reagents are:m1_m2_m3:CO, and Products are 0:COC1=CC=C(C=C1)C1=CC2=C(N=C(N=C2)N)N=C1NC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 3.4 g of 2-amino-7-chloro-6-(4-methoxyphenyl)-pyrido[2,3-d]pyrimidine from Example 12, 40 mL of anhydrous methylamine, and 10 mL of methanol were heated in a bomb on a steam bath for 4 hours. After cooling, the suspension was washed out of the bomb with 50 mL of methanol/water (50:50) and the solvents were evaporated in vacuo. The solid residue was slurried with 50 mL of water, filtered, and crystallized from ethanol to afford 2.2 g of the title compound 6-(4-methoxyphenyl)-N7 -methyl-pyrido[2,3-d]pyrimidine-2,7-diamine, mp 270°-275° C. dec. |
Here is a chemical reaction formula: Reactants are:m2:[H][H];m1_m6_m7:BrC1=C(C(=CC(=N1)N)N)C#N;m3_m4:C(C)(=O)[O-].[K+];m3_m4:CO;m5:[H][H], Reagents are:m1_m6_m7:[Pd];m1_m6_m7:O1CCCC1, and Products are 0:NC1=NC=C(C(=C1)N)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A suspension of 21.3 g of 6-bromo-2,4-diamino-5-cyanopyridine (JACS, 80:2838-2840 (1958)) and 1 g of 20% palladium on charcoal in 250 mL of tetrahydrofuran was shaken in a Parr apparatus under an atmosphere hydrogen. After 2 hours, the reaction was stopped and 10 g of potassium acetate and 50 mL of methanol added. The reaction was recharged with hydrogen and shaken for 18 hours. The solvents were removed under reduced pressure and the residue crystallized from isopropyl alcohol to afford the title compound 2,4-diamino-5-cyanopyridine, mp 201°-202° C. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m5:NC1=NC=C(C(=C1)N)C#N;m1_m4_m2_m5:C(=O)O;m3:[H][H], Reagents are:m1_m4_m2_m5:[Ni];m1_m4_m2_m5:O, and Products are 0:NC1=C(C=O)C(=CC=N1)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A suspension of 13.4 g of 2,4-diamino-5-cyanopyridine from Example 14, 2 g of Raney nickel catalyst, 40 mL of 97-100% formic acid, and 80 mL of water were shaken in a Parr apparatus under an atmosphere of nitrogen until the requisite amount of hydrogen was consumed. The solvents were removed under reduced pressure and the residue treated with 17 mL of concentrate HCl. The resulting pink solid was slurried in a small amount of water, filtered, washed with isopropyl alcohol, followed by diethylether, and dried. Crystallization from ethanol afforded 6.5 g of the title compound 2,4-diaminonicotinaldehyde. |
Here is a chemical reaction formula: Reactants are:m4:C;m3:C(C)(C)(C)N=C=O;m1_m5_m2:NC=1C(=CC2=C(N=C(N=C2)NCCCN(CC)CC)N1)C1=C(C=CC=C1Cl)Cl;m1_m5_m2:[H-].[Na+], Reagents are:m6:O;m1_m5_m2:CN(C)C=O, and Products are 0:C(C)(C)(C)NC(=O)NC=1C(=CC2=C(N=C(N=C2)NCCCN(CC)CC)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (0.48 g) from Example 20 in DMF (5 mL) was added 60% sodium hydride suspension (46 mg), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture was added t-butyl isocyanate (0.113 g), and the mixture was stirred for 18 hours. The reaction mixture was diluted with water and the insoluble material was collected by filtration. The solid was suspended in water (20 mL) and acidified with 1.0N HCl to form a solution. Activated charcoal was added to the solution, and the suspension filtered through celite, washing with water. The filtrate was made basic with 1.0N NaOH, and the insoluble product was collected by filtration and washed with water. A 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column, eluting with a solvent gradient starting from 86% of 0.1% trifluoroacetic acid in water/14% acetonitrile to 14% of 0.1% trifluoroacetic acid in water/86% acetonitrile over a 22-minute time period to afford 165 mg of 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, mp dec >80° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m1_m2:C(C)N=C=O, Reagents are:, and Products are 0:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)NC(=O)NCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2,7-Diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine was reacted with ethyl isocyanate according to the general procedure of Example 2. The crude product was purified by radial chromatography eluting with a gradient of 70% ethyl acetate/30% chloroform to 100% chloroform to give the title compound, 1-[2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea, mp 185°-187° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m1_m2:C(CCC)N=C=O, Reagents are:, and Products are 0:C(CCC)NC(=O)NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)NC(=O)NCCCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 0.5 g 2,7-Diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine from Example 1 and 15 mL of n-butyl isocyanate is refluxed for 2 hours. The reaction mixture is allowed to cool to room temperature and the insoluble material filtered. The solid is recrystallized several times from ethanol to give the title compound; mp 200°-202° C. |
Here is a chemical reaction formula: Reactants are:m1:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m2:CN(CCCN)C, Reagents are:, and Products are 0:NC=1C(=CC2=C(N=C(N=C2)NCCCN(C)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The title compound was prepared as in Example 20 by reacting 3.0 g of 2,7-diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine from Example 1 and 60 mL of 3-(dimethylamino)propylamine to give the title compound. |
Here is a chemical reaction formula: Reactants are:m2:C(C)(C)(C)N=C=O;m1:NC=1C(=CC2=C(N=C(N=C2)NCCCN(C)C)N1)C1=C(C=CC=C1Cl)Cl, Reagents are:, and Products are 0:C(C)(C)(C)NC(=O)NC=1C(=CC2=C(N=C(N=C2)NCCCN(C)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the procedure of Example 21, 1.62 g of 7-amino-6-(2,6-dichlorophenyl)-2-(3-dimethylamino-propylamino)-pyrido[2,3-d]pyrimidine from Example 27 was reacted with 0.48 g of t-butyl isocyanate to give the title compound; mp gradually dec above 130° C. |
Here is a chemical reaction formula: Reactants are:m1:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m2:CN(CC(CN)(C)C)C, Reagents are:, and Products are 0:NC=1C(=CC2=C(N=C(N=C2)NCC(CN(C)C)(C)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The title compound was prepared as described above in Example 20 by reacting 2.0 g of 2,7-diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine from Example 1 and 15 mL of N,N,2,2-tetramethyl-1,3-propanediamine. |
Here is a chemical reaction formula: Reactants are:m2:C(C)(C)(C)N=C=O;m1:NC=1C(=CC2=C(N=C(N=C2)NCC(CN(C)C)(C)C)N1)C1=C(C=CC=C1Cl)Cl, Reagents are:, and Products are 0:C(C)(C)(C)NC(=O)NC=1C(=CC2=C(N=C(N=C2)NCC(CN(C)C)(C)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the procedure of Example 21, 1.0 g of 7-amino-6-(2,6-dichlorophenyl)-2-(3-dimethylamino-2,2-dimethyl-propylamino)-pyrido[2,3-d]pyrimidine from Example 29 was reacted with 0.26 g of t-butyl isocyanate to give the title compound; mp 161°-170° C. |
Here is a chemical reaction formula: Reactants are:m1:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m2:NCCCCN1CCN(CC1)C, Reagents are:, and Products are 0:NC=1C(=CC2=C(N=C(N=C2)NCCCCN2CCN(CC2)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the procedure of Example 20, 2.0 g of 2,7-diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine from Example 1 was reacted with 15 mL of 1-(4-aminobutyl)-4-methyl-piperazine to give the title compound. |
Here is a chemical reaction formula: Reactants are:m4:C([O-])(O)=O.[Na+];m1_m2_m3:NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N;m1_m2_m3:S(N)(O)(=O)=O;m1_m2_m3:NCCCN1CCN(CC1)C, Reagents are:m5:O, and Products are 0:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NCCCN2CCN(CC2)C)N=C1N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 2,7-diamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidine (3.0 g) from Example 1, sulfamic acid (1.9 g), and 1-(3-aminopropyl)-4-methylpiperazine (15 mL) was heated to approximately 150° C. for 24 hours. After cooling, the residue was dissolved in water. The aqueous solution was made alkaline with a solution of saturated sodium bicarbonate and extracted with dichloromethane several times. The dichloromethane layers were combined, dried over magnesium sulfate, and concentrated in vacuo. The residue was recrystallized from ethyl acetate to give 2.0 g of 6-(2,6-dichlorophenyl)-N2 -[3-(4-methyl-piperazin-1-yl)-propyl]-pyrido[2,3-d]pyrimidine-2,7-diamine, CIMS (1% NH3 in CH4): 474=M+ +C2H5, 446=M+ +H (Base); mp 208°-211° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NCCCN2CCN(CC2)C)N=C1N;m1_m2:C(C1=CC=CC=C1)N=C=O, Reagents are:m0_m3:CO.CC#N, and Products are 0:C(C1=CC=CC=C1)NC(=O)NC=1C(=CC2=C(N=C(N=C2)NCCCN2CCN(CC2)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 6-(2,6-Dichlorophenyl)-N2 -[3-(4-methyl-piperazin-1-yl)-propyl]-pyrido[2,3-d]pyrimidine-2,7-diamine (1.08 g) from Example 36 was reacted with 0.298 g of benzyl isocyanate according to the general procedure of Example 37 to give 0.822 g of 1-benzyl-3-{6-(2,6-dichlorophenyl)-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrido[2,3-d]pyrimidin-7-yl}-urea, ESMS (20/80 MeOH/CH3CN+0.1% AcOH): M+ +H=579; mp 144°-148.5° C. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)NCCCN2CCN(CC2)C)N=C1N;m1_m2:C(C=C)N=C=O, Reagents are:, and Products are 0:C(C=C)NC(=O)NC=1C(=CC2=C(N=C(N=C2)NCCCN2CCN(CC2)C)N1)C1=C(C=CC=C1Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 6-(2,6-Dichlorophenyl)-N2 -[3-(4-methyl-piperazin-1-yl)-propyl]-pyrido[2,3-d]pyrimidine-2,7-diamine (1.0 g) from Example 36 was reacted with 0.186 g of allyl isocyanate according to the general procedure of Example 37. The product was purified by chromatography and crystallized from ethyl acetate to give 0.31 g of 1-allyl-3-{6-(2,6-dichlorophenyl)-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrido[2,3-d]pyrimidin-7-yl}-urea, ESMS (20/80 MeOH/CH3CN+0.1% AcOH): M+ +H=529 (Base), 472, 446; mp 104°-108° C. |