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

HRID 468772Notes

Reaction equation

HRID 468772 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c6019c1607ed435ab3b1583c93e78f91
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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