反应详情

LiOH.H2O (32 mg, 0.76 mmol) was added to a stirred mixture of 3-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-1H-pyrazol-3-yl)-benzoic acid methyl ester (99 mg, 0.2 mmol) (prepared by the method used for the synthesis of Example 102, starting, alternatively from methyl 3-acetylbenzoate to generate the 1H-pyrazole intermediate) in THF:MeOH:H2O (3:2:1, 38 mL) was added, and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated under reduced pressure Cold water was then added and the contents were acidified with 10% aqueous HCl, the precipitate was filtered. The solid obtained was purified by recrystallisation form methanol to afford 50 mg (38.1% Yield) of 3-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-2H-pyrazol-3-yl)-benzoic acid. LC/MS [M+H]+: 517, 95.29%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 13.2 (s, 1H), 8.38 (s, 1H), 8.04 (d, 1H), 7.9 (d, 1H), 7.5 (m, 2H), 7.26 (t, 3H), 7.18 (bs, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 2H), 1.9 (m, 2H), 1.6 (m, 2H).

1. customprepared by the method
2. customused for the synthesis of Example 102
3. additionwas added
4. concentrationThe reaction mixture was concentrated under reduced pressure Cold water
5. additionwas then added
6. filtrationthe precipitate was filtered
7. customThe solid obtained
8. customwas purified by recrystallisation
9. customform methanol