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

HRID 1502252Notes

Reaction equation

HRID 1502252 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e56c98e02eee40cc977b488ca42cceb9
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

Loading…