反应详情

DIPEA (170 mg, 1.3 mmol) was added to a stirred solution of N-biphenyl-4-yl-malonamic acid (100 mg, 0.4 mmol) in DMF (2.0 mL) followed by HOBt (81 mg, 0.6 mmol) and EDCI.HCl (114 mg, 0.6 mmol). After 2 minutes of stirring, 4-(3,4,5-trifluoro-phenoxy)-piperidine hydrochloride (100 mg, 0.4 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethylacetate, washed with brine and concentrated. The remaining residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3) to afford 30 mg (17% Yield) of N-biphenyl-4-yl-3-oxo-3-[4-(3,4,5-trifluoro-phenoxy)-piperidin-1-yl]-propionamide. LC/MS [M+H]+: 469.17, 98.06%, 1H NMR (300 MHz, DMSO-d6): δ7.6 (m, 6H), 7.4 (m, 2H), 7.3 (m, 1H), 7.1 (m, 2H), 4.6 (m, 1H), 3.9 (m, 1H), 3.8 (m, 1H), 3.6 (m, 2H), 3.4 (m, 1H), 3.2 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.5 (m, 1H).

1. additionwas added
2. stirringstirring
3. waitwas continued at ambient temperature overnight
4. extractionextracted with ethylacetate
5. washwashed with brine
6. concentrationconcentrated
7. customThe remaining residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3)