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

HRID 1502290노트

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HRID 1502290 반응식
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

참가 물질

7

반응물 4

HCID 674Dimethylamine2회HCID 6228DimethylformamideHCID 8471TriethylamineHCID 866749394-(1-bromoethyl)-N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)benzamide

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

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온도
40 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6780e342c667437fae0f8be5365f4d2e
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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