4-Aminotetrahydropyran → 6-[3-(3,4-Difluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(tetrahydro-pyran-4-yl)-nicotinamide

Participants

Reaction Conditions

Reaction Steps

A trimethylaluminium solution (2 M in toluene, 532 μL, 1.06 mmol) was added to a solution of 4-aminotetrahydropyran (111 mg, 1.06 mmol) in dioxane (5 mL). 6-[3-(3,4-Difluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.27 mmol) in dioxane (5 mL) was added after 1 h at 50° C. The reaction mixture was stirred at 85° C. overnight. Again trimethylaluminium solution (2 M in toluene, 500 μL, 1.0 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, dichloromethane:methanol=100:0 to 95:5) to afford the title compound (60 mg, 50%) as a white solid. MS: m/e=446.4 [M+H]+.

Provenance & Evidence