Pyridine → N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-phenylcyclopropanecarboxamide

반응식

[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:19])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.C(Cl)Cl.N1C=CC=CC=1.[C:29]1([C@@H:35]2[CH2:37][C@H:36]2[C:38](Cl)=[O:39])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:19])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:38]([CH:36]4[CH2:37][CH:35]4[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:39])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1

참가 물질

반응물 4

HCID 1049Pyridine

HCID 6344Dichloromethane

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chloride

HCID 574102447-(5-Fluoro-2-methylphenyl)isoquinolin-3-amine

생성물 1

HCID 67974788N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-phenylcyclopropanecarboxamide수율 37%

실험 절차

To a mixture of 7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine (50.5 mg, 0.200 mmol) in methylene chloride (2.0 mL, 31 mmol) was added pyridine (0.04 mL, 0.5 mmol) and trans-2-phenyl-1-cyclopropanecarbonyl chloride (35.0 uL, 0.225 mmol). The reaction mixture was stirred at room temperature for one hour and then evaporated in vacuo. The resulting residue was purified via reverse phase HPLC and lyophilized to yield 29.1 mg (37%) of N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-phenylcyclopropanecarboxamide (mixture of trans stereoisomers). LCMS (ESI): RT (min)=6.288, M+H=397.1, Method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 9.17 (s, 1H), 8.54 (s, 1H), 8.04 (s, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.72 (d, J=8.5 Hz, 1H), 7.38 (t, J=7.0 Hz, 1H), 7.31 (t, J=7.6 Hz, 2H), 7.25-7.12 (m, 5H), 2.47-2.40 (m, 2H), 2.25 (s, 3H), 1.60-1.48 (m, 1H), 1.39 (dd, J=11.0, 7.4 Hz, 1H).