3-Fluoroacetophenone → 5-(3-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

Participants

Reaction Steps

DIPEA (253 mg, 1.96 mmol) was added to a stirred solution 5-(3-fluoro-phenyl)-isoxazole-3-carboxylic acid (81 mg, 0.39 mmol) (prepared by the method used for the synthesis of Intermediate 25, starting from 3′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (56 mg, 0.41 mmol) and EDCI.HCl (79 mg, 0.41 mmol). After 2 minutes 2-amino-1-[4-(5-Chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochloride (120 mg, 0.38 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. Purification by recrystallisation from 1% methanol in ethyl acetate to afford 35 mg (19.5% Yield) of 5-(3-fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 459, 100%. 1H NMR (300 MHz, DMSO-d6): δ 8.7 (t, 1H), 8.32 (d, 1H), 8.22 (s, 1H), 7.78 (t, 2H), 7.72 (s, 1H), 7.58 (m, 1H), 7.5 (s, 1H), 7.36 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 2H), 3.4 (m, 1H), 3.2 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

Provenance & Evidence