Hydrochloric Acid → HCID 71115178, compound

Participants

Reaction Steps

To a solution of tert-butyl 3-(4-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenylcarbamoyl)phenyl)pyrrolidine-1-carboxylate (prepared following the procedures described for Example 15) (0.135 mmol) in methylene chloride (3.0 mL, 47 mmol) was added 4.0 M of hydrogen chloride in 1,4-dioxane (0.50 mL). The reaction mixture was stirred at room temperature for three hours, and then evaporated in vacuo. To this crude product was added potassium carbonate (53.6 mg, 0.388 mmol), N,N-dimethylformamide (3.0 mL, 39 mmol), and methyl iodide (9.0 uL, 0.14 mmol). The reaction mixture was stirred at room temperature for 18 hours, and then potassium carbonate (33.1 mg, 0.239 mmol) and methyl iodide (7.0 uL, 0.11 mmol) were added. The reaction mixture was stirred at room temperature for 24 hours, and then poured into ethyl acetate, washed with 2M aqueous Na2CO3, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 5-20% 1M NH3/MeOH in dichloromethane) to yield 6.0 mg (9%) of N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-methylpyrrolidin-3-yl)benzamide. LCMS (ESI): RT (min)=4.104, M+H=505.2, method=E; 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 10.18 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.02 (s, 1H), 7.92 (t, J=9.3 Hz, 3H), 7.81-7.67 (m, 3H), 7.44 (d, J=8.1 Hz, 2H), 7.32 (d, J=8.4 Hz, 1H), 3.52-3.40 (m, 2H), 3.01 (unresolved, 1H), 2.82 (unresolved, 2H), 2.44 (s, 3H), 2.26 (s, 3H), 2.08 (m, 1H), 1.84 (m, 2H), 0.85 (m, 4H).

Provenance & Evidence