Dimethylformamide → N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide

HRID 468754ノート

反応式

HRID 468754 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:31])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19](=O)[O:20]C4C=CC([N+]([O-])=O)=CC=4)[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.CN(C)C=O.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:31])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([N:41]4[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1

参加物

5

反応物 3

HCID 6228DimethylformamideHCID 531671-MethylpiperazineHCID 679748684-Nitrophenyl 7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylcarbamate

生成物 1

HCID 67974856N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide収率 4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

4-nitrophenyl 7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylcarbamate (0.156 g, 0.374 mmol) was dissolved in N,N-dimethylformamide (2.0 mL, 26 mmol) and 1-methyl-piperazine (0.20 mL, 1.8 mmol) was added. The reaction mixture was heated at 90° C. for 1 hour. The reaction mixture was then diluted with dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-20% methanol in dichloromethane with 2% triethylamine) followed by reverse phase HPLC and lyophilization to yield 5.4 mg (4%) of N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide. LCMS (ESI): RT (min)=4.017, M+H=379.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 9.12 (s, 1H), 8.23 (s, 1H), 7.99 (s, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.38 (s, 1H), 7.16 (t, J=8.3 Hz, 2H), 3.52 (s, 4H), 2.33 (s, 4H), 2.25 (s, 3H), 2.21 (s, 3H).

後処理

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialdried over MgSO4
  3. customevaporated in vacuo
  4. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-20% methanol in dichloromethane with 2% triethylamine)

出典と根拠

ORDレコード
ord-b8acf88ba5624bb791fcfab721b65b8a
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

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