Reaction Steps
rac-(4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-4,4a,5,6,7,13 b-hexahydro-1H-benzo[3,4]cyclohepta[1,2-d]imidazo[1,5-a]pyridin-3 (2H)-one (149, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.291 g, 0.662 mmol) was suspended in DME (7 mL) then CsF (0.060 g, 0.397 mmol) was added. The mixture was cooled to about −10° C. then trimethyl(trifluoromethyl)silane (0.185 g, 1.30 mmol) was added. After 15 min TBAF (1 M in THF) (0.695 mL, 0.695 mmol) was added and the mixture was allowed to warm to rt. The mixture was concentrated under reduced pressure then water (25 mL) was added to the material and the resulting solids collected by filtration. The material was purified on silica gel (12 g) using a gradient from 0-10% MeOH in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-(3R,4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-3-(trifluoromethyl)-2,3,4,4a,5,6,7,13b-octahydro-1H-benzo[3,4]cyclohepta[1,2-d]imidazo[1,5-a]pyridin-3-ol (151, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Trifluoromethyl) (0.185 g, 55%); LC/MS, method 2, Rt=2.54 min, MS m/z 510 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.39-8.37 (m, 1H), 8.18 (s, 1H), 7.98-7.89 (m, 3H), 7.74 (s, 1H), 7.40-7.36 (m, 1H), 7.27-7.18 (m, 2H), 7.09-7.03 (m, 1H), 6.47 (d, J=7.8 Hz, 1H), 5.97 (s, 1H), 3.59 (d, J=13.2 Hz, 1H), 3.43-3.32 (m, 1H), 3.15 (d, J=13.4 Hz, 1H), 3.08-3.03 (m, 1H), 2.23-2.17 (m, 1H), 2.13-2.07 (m, 1H), 2.04-1.86 (m, 3H), 1.83-1.67 (m, 5H), 1.46-1.36 (m, 1H).
