反应详情

温度

50 °C

To a mixture of 7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine (103.2 mg, 0.4090 mmol), 2,2-difluorocyclopropanecarboxylic acid (79.6 mg, 0.652 mmol) and (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (326.5 mg, 0.6298 mmol) in N,N-dimethylformamide (2 mL, 20 mmol) was added N,N-diisopropylethylamine (0.25 mL, 1.4 mmol) and 4-dimethylaminopyridine (6.7 mg, 0.055 mmol). The reaction mixture was stirred at 50° C. for 2.5 hours. The reaction mixture was then poured into ethyl acetate, which was washed with two portions water, dried with brine and MgSO4, and filtered through a plug of silica gel, which was rinsed with ethyl acetate, and evaporated in vacuo. The resulting residue was purified via reverse phase HPLC and lyophilized to yield 106.4 mg (73%) of 2,2-difluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=5.701, M+H=357.1, Method=E; 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 9.21 (s, 1H), 8.50 (s, 1H), 8.07 (s, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.39 (s, 1H), 7.18 (d, J=8.7 Hz, 2H), 3.07 (d, J=10.0 Hz, 1H), 2.25 (s, 3H), 2.07 (s, 2H).

1. washwas washed with two portions water
2. dry with materialdried with brine and MgSO4
3. filtrationfiltered through a plug of silica gel, which
4. washwas rinsed with ethyl acetate
5. customevaporated in vacuo
6. customThe resulting residue was purified via reverse phase HPLC