Dimethylamine → Prepro-Atrial Natriuretic Factor (56-92) (human)

HRID 468772ノート

反応式

HRID 468772 の反応式
Br[CH:2]([C:4]1[CH:35]=[CH:34][C:7]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[C:13]([C:18]3[CH:27]=[C:26]4[C:21]([CH:22]=[C:23]([NH:28][C:29]([CH:31]5[CH2:33][CH2:32]5)=[O:30])[N:24]=[CH:25]4)=[CH:20][CH:19]=3)[CH:12]=2)=[O:9])=[CH:6][CH:5]=1)[CH3:3].[CH3:36][NH:37][CH3:38].C(N(CC)CC)C.CN(C)C=O>O1CCCC1.ClCCl>[CH:31]1([C:29]([NH:28][C:23]2[N:24]=[CH:25][C:26]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[C:18]([C:13]2[CH:12]=[C:11]([NH:10][C:8](=[O:9])[C:7]4[CH:34]=[CH:35][C:4]([CH:2]([N:37]([CH3:38])[CH3:36])[CH3:3])=[CH:5][CH:6]=4)[CH:16]=[CH:15][C:14]=2[CH3:17])[CH:27]=3)=[O:30])[CH2:33][CH2:32]1

参加物

7

反応物 4

HCID 674Dimethylamine2 回HCID 6228DimethylformamideHCID 8471TriethylamineHCID 866749394-(1-bromoethyl)-N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)benzamide

生成物 1

HCID 71115074Prepro-Atrial Natriuretic Factor (56-92) (human)収率 22%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
40 °C

実験手順

To the crude reaction mixture from Step 2 was added 2.0 M of dimethylamine in tetrahydrofuran (0.15 mL). The resulting mixture was then stirred at 40° C. After 1.5 hours, 2.0 M of dimethylamine in tetrahydrofuran (0.20 mL), triethylamine (0.05 mL, 0.4 mmol), and 1 mL N,N-dimethylformamide were added and the reaction mixture was heated at 50° C. After an additional hour, the reaction was poured into dichloromethane and washed once with saturated aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 17.6 mg (22%) of N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-(dimethylamino)ethyl)benzamide. LCMS (ESI): RT (min)=4.090, M+H=493.2, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 10.20 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.02 (s, 1H), 7.92 (overlapping, 3H), 7.79 (d, J=1.9 Hz, 1H), 7.77-7.67 (m, 2H), 7.44 (d, J=8.2 Hz, 2H), 7.32 (d, J=8.4 Hz, 1H), 3.35 (q, J=6.8 Hz, 1H), 2.26 (s, 3H), 2.11 (s, 7H), 1.29 (d, J=6.7 Hz, 3H), 0.85 (m, 4H).

後処理

  1. temperaturethe reaction mixture was heated at 50° C
  2. waitAfter an additional hour
  3. washwashed once with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified via reverse phase HPLC

出典と根拠

ORDレコード
ord-c6019c1607ed435ab3b1583c93e78f91
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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