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

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).

1. customprepared by the method
2. additionwas added to the reaction mixture
3. extractionextracted with ethyl acetate
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customPurification
7. customby recrystallisation from 1% methanol in ethyl acetate

ORD record

ord-cf8580a63a744e0d91ef19cfbcf82775

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129376B2