反应详情

To a mixture of 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]ethanone (0.045 g, 0.10 mmol) and NaH (0.030 g, 0.75 mmol, 60% in mineral oil) in DMF (0.8 mL) was added dry paraformaldehyde (0.015 g, 0.50 mmol). The mixture was stirred at rt for 30 min. It was then quenched with water. The mixture was partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo, and purified by reverse phase HPLC to afford the desired product (0.006 g, 12%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.44 (dd, J=8.8, 4.6 Hz, 2H), 7.16 (dd, J=8.4, 8.4 Hz, 2H), 5.51 (dd, J=8.0, 7.2 Hz, 1H), 4.18 (m, 1H), 4.08 (m, 1H), 3.75 (m, 1H), 3.37 (s, 3H), 3.35 (m, 1H), 2.78 (m, 2H), 2.33 (s, 3H), 2.09 (m, 2H); MS: (ES) m/z calculated for C21H20ClF4N5O2 [M+H]+ 486.1, found 486.1.

1. customIt was then quenched with water
2. customThe mixture was partitioned between EtOAc (50 mL) and brine (30 mL)
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. custompurified by reverse phase HPLC