Toluene → N-Cyclopropylmethyl-6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinamide

Participants

Reaction Conditions

Reaction Steps

A trimethylaluminium solution (2 M in toluene, 418 μL, 0.84 mmol) was added to a solution of aminomethylcyclopropane (61.3 mg, 0.84 mmol) in dioxane (3.75 mL). 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (75.0 mg, 0.21 mmol) in dioxane (3.75 mL) was added after 1 h at 50° C. The reaction mixture was stirred at 85° C. overnight. Again trimethylaluminium solution in toluene (2 M in toluene, 418 μL, 0.84 mmol) was added and stirring was continued for 3 h at 85° C. The solvent was removed by distillation. The residue was purified by chromatography (silica, ethyl acetate:heptane=4:6 to 8:2) to yield the title compound (30 mg, 36%) as a light yellow solid. MS: m/e=398.2 [M+H]+.

Provenance & Evidence