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

HRID 1502290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502290
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

Komponenten

7

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-6780e342c667437fae0f8be5365f4d2e
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

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