Methyl iodide → 4-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid (2-methoxy-pyridin-3-yl)-methyl-amide

Participants

Reaction Steps

To a solution of 50 mg (0.17 mmol) (4-(2,5-dichloro-phenoxy)-pyrimidine-5-carboxylic acid (Example 76, intermediate a) in 1.5 mL dichloromethane were added 0.05 mL (0.34 mmol) triethylamine and 49 mg (0.19 mmol) 2-chloro-1-methylpyridinium iodide. After stirring at room temperature for 20 minutes, 24 mg (0.19 mmol) 2-methoxypyridin-3-amine (commercially available, CAS RN 20265-38-7) were added. After 2 hours, the reaction mixture was poured on water and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered and evaporated. The crude product was dissolved in 1 mL N,N-dimethylformamide and 14 mg (0.35 mmol) sodium hydride (60% suspension in mineral oil) followed by 0.02 mL (0.35 mmol) of methyliodide were added. The reaction was stirred at 50° C. for 2 hours. The suspension was filtered using a syringe micro filter and purified on a preparative HPLC system (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 28 mg (39%) of the desired compound as a light brown solid. MS (ESI): m/z=405.0 [M+H]+.

Provenance & Evidence