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

DIPEA (328 mg, 2.5 mmol) to a stirred solution of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (150 mg, 0.724 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2′fluoroacetophenone) in DMF (5 mL) followed by HOBt (100 mg, 0.76 mmol) and EDCI.HCl (140 mg, 0.76 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone dihydrochloride (220 mg, 0.724 mmol) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, the precipitate was collected. The solid was purified by recrystallisation from ethyl acetate The residue obtained was again purified by column chromatography (using 60-120 silica gel and 60% EtOAc in hexane as eluent) to afford 88 mg (26.6% Yield) of 5-(2-fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 457, 91.47%. 1H NMR (300 MHz, DMSO-d6): δ8.75 (t, 1H), 8.0 (m, 1H), 7.6 (m, 1H), 7.38 (m, 2H), 7.1 (m, 3H), 6.82 (d, 1H), 6.6 (m, 1H), 4.8 (m, 1H), 4.3 (d, 1H), 4.1 (d, 2H), 3.8 (d, 1H), 3.6 (m, 1H), 3.1 (t, 1H), 2.8 (t, 1H), 1.9 (t, 2H), 1.45 (m, 2H).

1. customthe precipitate was collected
2. customThe solid was purified by recrystallisation from ethyl acetate The residue
3. customobtained
4. customwas again purified by column chromatography (using 60-120 silica gel and 60% EtOAc in hexane as eluent)

ORD-Eintrag

ord-8ea231cdd8364b5e86f080b2209e7415

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08129376B2