反应详情

A solution tert-butyl 2-(3-(4-(3,4-difluoro-2-(trifluoromethyl)phenyl)piperidine-1-carbonyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)acetate (53 mg, 0.10 mmol) in anhydrous CH2C12 (3 mL) was treated with TFA (3 mL) and stirred under an atmosphere of N2 at room temperature for 8 h. After this time, the mixture was concentrated to dryness under reduced pressure and solvent exchanged with CH2Cl2 (10 mL). The residue was diluted in anhydrous CH2Cl2 (10 mL), treated with MP-carbonate (0.50 g) and stirred at room temperature for 15 min. After this time, the solution was filtered and the resin washed with CH2C1 (2×10 mL). The filtrate was concentrated to dryness under reduced pressure to provide 2-(3-(4-(3,4-difluoro-2-(trifluoromethyl)phenyl)piperidine-1-carbonyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)acetic acid as an off-white solid (40 mg, 85%): mp 151-153° C.; 1H NMR (500 MHz, DMSO-d6) δ 13.29 (br s, 0.25H), 12.89 (br s, 0.75H), 7.56-7.55 (m, 1H), 7.51-7.50 (m, 1H), 4.87-4.86 (m, 1H), 4.66-4.64 (m, 1H), 4.04-4.02 (m, 2H), 3.76-3.72 (m, 2H), 3.34-3.32 (m, 2H, partially merged with H2O peak), 3.15-3.11 (m, 4H), 2.76-2.74 (m, 2H), 1.76-1.70 (m; 4H); ESI MS m/z 473 [M+H]+.

1. concentrationAfter this time, the mixture was concentrated to dryness under reduced pressure and solvent
2. additionThe residue was diluted in anhydrous CH2Cl2 (10 mL)
3. additiontreated with MP-carbonate (0.50 g)
4. stirringstirred at room temperature for 15 min
5. filtrationAfter this time, the solution was filtered
6. washthe resin washed with CH2C1 (2×10 mL)
7. concentrationThe filtrate was concentrated to dryness under reduced pressure