Formaldehyde → 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]-3-hydroxy-propan-1-one

Participants

Reaction Conditions

Reaction Steps

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 (0.100 g, 0.23 mmol) in THF (3 ml) at −78° C. was added LDA (0.15 mL, 0.3 mmol, 2 M in THF). After stirred for 10 min at −78° C., dry paraformaldehyde (0.020 g, 0.66 mmol, suspended in THF) was added. The mixture was then warmed to rt for 8 min, quenched with sat. NH4Cl. 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 yield the desired product (0.060 g, 56%). 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.43 (dd, J=8.4, 4.6 Hz, 2H), 7.17 (dd, J=8.8, 8.4 Hz, 2H), 5.40 (t, J=5.4 Hz, 1H), 4.90 (s, 1H), 4.30 (m, 1H), 4.20 (m, 1H), 3.71 (m, 1H), 3.29 (m, 1H), 2.79 (m, 2H), 2.28 (s, 3H), 1.95 (m, 2H); MS: (ES) m/z calculated for C20H18ClF4N5O2 [M+H]+ 472.1, found 472.1.

Provenance & Evidence