Water → N-Cyclopropylmethyl-6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinamide

A solution of trimethylaluminium (2 M in toluene, 529 μL, 1.1 mmol) was added dropwise (exothermic) to a solution of cyclopropanemethylamine (75 mg, 91 μL, 1.1 mmol) in dioxane (7 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (100 mg, 0.26 mmol) in dioxane (4 mL) was added. The resulting mixture was then heated at 85-95° C. for 6 h and then cooled to room temperature and then poured into water and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (92 mg, 83%) which was obtained as an off white solid. MS: m/e=418.3 [M+H]+.

1. temperatureThe resulting mixture was then heated at 85-95° C. for 6 h
2. temperaturecooled to room temperature
3. extractionextracted with ethyl acetate which
4. washwas then washed with brine
5. dry with materialdried over sodium sulfate
6. customevaporated
7. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1)

ORD-Eintrag

ord-82d554b7c1784a728f3ee8c733b0a09c

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846719B2