Pyridine → N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-methyl-1H-pyrazole-4-carboxamide

HRID 468732

反応式

HRID 468732 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.N1C=CC=CC=1.[CH3:31][N:32]1[CH:36]=[C:35]([C:37](Cl)=[O:38])[CH:34]=[N:33]1>ClCCl>[CH:21]1([C:19]([NH:18][C:13]2[N:14]=[CH:15][C:16]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[C:8]([C:6]2[CH:7]=[C:2]([NH:1][C:37]([C:35]4[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=4)=[O:38])[CH:3]=[CH:4][C:5]=2[CH3:24])[CH:17]=3)=[O:20])[CH2:22][CH2:23]1

参加物

5

反応物 3

HCID 1049PyridineHCID 31649311-methyl-1H-pyrazole-4-carbonyl chlorideHCID 67974803N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

生成物 1

HCID 71115294N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-methyl-1H-pyrazole-4-carboxamide収率 61%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide (53.8 mg, 0.144 mmol) in methylene chloride (2.0 mL, 31 mmol) was added pyridine (0.10 mL, 1.2 mmol) and 1-methyl-1H-pyrazole-4-carbonyl chloride (27.7 mg, 0.192 mmol). The reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was then poured into 50 mL dichloromethane, washed with aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 37.1 mg (61%) of N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-methyl-1H-pyrazole-4-carboxamide. LCMS (ESI): RT (min)=4.307, M+H=426.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.80 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.28 (s, 1H), 8.01 (d, J=4.9 Hz, 2H), 7.93 (d, J=8.6 Hz, 1H), 7.70 (dd, J=10.3, 4.6 Hz, 3H), 7.30 (d, J=8.0 Hz, 1H), 3.89 (s, 3H), 2.25 (s, 3H), 2.19-1.98 (m, 1H), 0.85 (m, 4H).

後処理

  1. washwashed with aqueous NaHCO3
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified via reverse phase HPLC

出典と根拠

ORDレコード
ord-8e563f5efb4c49199ff5fda28893e9a5
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

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