Water → N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (101 mg, 0.347 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (0.10 g, 0.44 mmol), potassium carbonate (147.9 mg, 1.070 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (24.3 mg, 0.0343 mmol) was added acetonitrile (3 mL, 60 mmol) and water (0.3 mL, 20 mmol). The reaction mixture was then stirred in a sealed vial at 90° C. for 8 hours, and then cooled to room temperature. The reaction mixture was poured into dichloromethane, washed once with saturated aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The resulting residue was purified via reverse phase HPLC and lyophilized to yield 22.7 mg (21%) of N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.328, M+H=310.0, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.20 (s, 1H), 8.60 (s, 1H), 8.45 (s, 1H), 8.24 (dd, J=8.7, 1.5 Hz, 1H), 8.08 (s, 1H), 7.90 (d, J=8.7 Hz, 1H), 2.76 (s, 3H), 2.08 (ddd, J=12.2, 7.8, 4.7 Hz, 1H), 0.85 (dd, J=9.3, 6.3 Hz, 4H).

Provenance & Evidence