Tetrahydrofuran → N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)morpholine-4-carboxamide

HRID 468734

反応式

HRID 468734 の反応式
[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([NH:24][C:25](=O)[O:26]C4C=CC([N+]([O-])=O)=CC=4)[CH:20]=[CH:21][C:22]=2[CH3:23])[CH:11]=3)=[O:5])[CH2:3][CH2:2]1.O1CCCC1.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C(N(CC)CC)C>C(OCC)(=O)C>[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[O:26])[CH:20]=[CH:21][C:22]=2[CH3:23])[CH:11]=3)=[O:5])[CH2:2][CH2:3]1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 8471TriethylamineHCID 679743514-Nitrophenyl 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamate

生成物 1

HCID 67977257N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)morpholine-4-carboxamide収率 67.5%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 4-nitrophenyl 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamate (55.5 mg, 0.115 mmol) in tetrahydrofuran (1.5 mL, 18 mmol) was added morpholine (0.0500 mL, 0.573 mmol) and triethylamine (0.0500 mL, 0.359 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 33.4 mg (67%) of N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)morpholine-4-carboxamide. LCMS (ESI): RT (min)=4.234, M+H=431.2, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.88 (s, 1H), 9.17 (s, 1H), 8.52 (s, 1H), 8.48 (s, 1H), 7.97 (s, 1H), 7.90 (d, J=8.6 Hz, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.46 (s, 1H), 7.43 (d, J=8.3 Hz, 1H), 7.20 (d, J=8.3 Hz, 1H), 3.66-3.53 (m, 4H), 3.47-3.37 (m, 4H), 2.21 (s, 3H), 2.15-2.00 (m, 1H), 0.98-0.67 (m, 4H).

後処理

  1. washwashed with saturated aqueous sodium bicarbonate and brine
  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-26f17a94b8d146cfb8117014189686d9
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

関連ノート

読み込み中…