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

反応式

[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

参加物

反応物 4

HCID 1049Pyridine

HCID 6344Dichloromethane

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

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

生成物 1

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

実験手順

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).