Sodium hydride → 8-(4-Fluorophenyl)-1-(isoxazol-3-ylmethyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

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Reaction Conditions

Reaction Steps

To a solution of 8-(4-fluorophenyl)-N,N,2-trimethyl-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide (50.0 mg, 0.141 mmol, Step 8 of Example 8) in N,N-dimethylformamide (1.4 mL), was added sodium hydride (6.7 mg, 0.17 mmol) at 0° C. and the mixture was stirred at 0° C. for 30 minutes. Then a solution of 3-(bromomethyl)isoxazole in N,N-dimethylformamide (1.0 mL, Step 1) was added to the mixture at 0° C. The mixture was allowed to warm to room temperature, stirred for 4 hours and left at the same temperature overnight. The reaction was quenched by saturated ammonium chloride aqueous solution. The mixture was extracted twice with ethyl acetate. The combined organic layer was washed with water and brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC eluting with hexane/ethyl acetate (1:1, twice), then dichloromethane/methanol (20:1, twice) to afford the title compound as a pale yellow solid (23.5 mg, 38%).

Provenance & Evidence