1,2-Dichloroethane → 4-Nitrophenyl 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamate

HRID 1502251Notes

Reaction equation

HRID 1502251 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.ClCCCl.N1C=CC=CC=1.Cl[C:36]([O:38][C:39]1[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=1)=[O:37]>>[CH:21]1([C:19]([NH:18][C:13]2[N:14]=[CH:15][C:16]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[C:8]([C:6]2[CH:7]=[C:2]([NH:1][C:36](=[O:37])[O:38][C:39]4[CH:40]=[CH:41][C:42]([N+:45]([O-:47])=[O:46])=[CH:43][CH:44]=4)[CH:3]=[CH:4][C:5]=2[CH3:24])[CH:17]=3)=[O:20])[CH2:22][CH2:23]1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 1049Pyridine2×HCID 821294-Nitrophenyl chloroformate2×HCID 67974803N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 679743514-Nitrophenyl 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamateYield 38.4%

Procedure

To a suspension of N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide (196.8 mg, 0.6201 mmol) in 1,2-dichloroethane (6.0 mL, 76 mmol) was added pyridine (0.15 mL, 1.8 mmol) and p-nitrophenyl chloroformate (0.1406 g, 0.6975 mmol). The reaction mixture was stirred at room temperature for 2 hours and then pyridine (0.15 mL, 1.8 mmol) and p-nitrophenyl chloroformate (131.9 mg, 0.6544 mmol) were added. After an additional hour at room temperature, the reaction mixture was evaporated in vacuo and purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-100% ethyl acetate in heptanes) to yield 114.8 mg (38%) of 4-nitrophenyl 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamate. LCMS (ESI): M+H=483.2; 1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 9.16 (s, 1H), 8.47 (s, 1H), 8.10 (d, J=9.0 Hz, 2H), 7.92 (s, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.63 (d, J=8.5 Hz, 1H), 6.97 (d, J=8.7 Hz, 1H), 6.90 (d, J=8.9 Hz, 2H), 6.54 (d, J=5.8 Hz, 2H), 2.14-2.02 (m, 4H), 0.85 (m, 4H).

Workup

  1. waitAfter an additional hour at room temperature
  2. customthe reaction mixture was evaporated in vacuo
  3. custompurified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-26c86199552e4a0bab0a3aa845fbb900
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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