反应详情

DIPEA (133 mg, 1.03 mmol) was added to a stirred solution of 5-(3-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid (60 mg, 0.294 mmol) (prepared from 5-(3-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester) in DMF (2 mL) followed by HOBt (41.7 mg, 0.308 mmol) and EDCI.HCl (59 mg, 0.308 mmol). After 2 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (99 mg, 0.294 mmol) 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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford the residue. Washing with ethyl acetate afforded 74 mg (51.7% Yield) of 5-(3-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 489, 96%. 1H NMR (300 MHz, DMSO-d6): δ13.6 (s, 1H), 9.6 (s, 1H), 8.0 (t, 1H), 7.5 (t, 1H), 7.1 (m, 7H), 6.9 (d, 1H), 6.8 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 2H), 2.0 (m, 2H), 1.6 (m, 2H).

1. additionwas added to the reaction mixture
2. extractionextracted with ethyl acetate
3. dry with materialdried over sodium sulfate
4. concentrationThe organic layer was concentrated under reduced pressure
5. customto afford the residue
6. washWashing with ethyl acetate