Acetic Acid → HCID 67218510, compound

Participants

Reaction Steps

A mixture of N-cyclopropyl-6-(1,2,3,6-tetrahydropyridin-4-yl)picolinamide free base (5b) (133 mg, 0.545 mmol), 3-(trifluoromethyl)isoxazole-5-carbaldehyde (75) (270 mg, 0.818 mmol) and acetic acid (0.037 ml, 0.654 mmol) in tetrahydrofuran (5 ml) was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (347 mg, 1.636 mmol) was added to the reaction mixture and stirred at room temperature for 15 hours. The reaction was quenched with saturated NaHCO3 solution (10 ml), extracted with ethyl acetate (50 ml×3), washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane: 75/25 to 85/15) to give the desired free base. This was diluted with ethyl acetate and HCl solution (4 N in 1,4-dioxane) was added to the solution. The resulted solid was triturated with hexane to give N-cyclopropyl-6-(1-((3-(trifluoromethyl)isoxazol-5-yl)methyl)-1,2,3,6-tetrahydropyridin-4-yl)picolinamide hydrochloride (76) (33 mg, yield 14%) as a pale yellow solid. 1H NMR (DMSO-d6): δ 8.52 (brs, 1H), 8.00 (m, 1H), 7.92 (m, 1H), 7.77 (m, 1H), 7.47 (m, 1H), 6.93 (s, 1H), 4.77 (m, 2H), 3.93 (m, 2H), 2.83-3.20 (m, 5H), 0.72 (m, 2H), 0.64 (m, 2H); MS: 393 (M+H+).

Provenance & Evidence