Reaction Steps
A solution of 2-(((3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)isothiazolidine 1,1-dioxide (35, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=Benzyl) (63 mg, 0.10 mmol) in DCM (3 mL) was cooled to about 0° C. and treated with BBr3 (0.40 mL, 0.40 mmol). The mixture was stirred for about 30 min, then the reaction was quenched by dropwise addition of MeOH (5 mL) and warmed to rt. The reaction was concentrated under reduced pressure, then dissolved in MeOH (5 mL) and stirred at 35° C. for about 15 min. DCM (5 mL) was added and the mixture was concentrated onto silica gel (1 g). The residue was purified on silica gel column (4 g) using a gradient of 30-100% EtOAc in DCM. Product fractions were combined and concentrated. The residue was dissolved in MeOH (5 mL) and water (3 mL), then concentrate under reduced pressure to about (3 mL) volume. The product was filtered off and dried under reduced pressure to yield 2-(((3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)isothiazolidine 1,1-dioxide (11, R1=4-Fluorophenyl, R2=1,1-dioxidoisothiazolidin-2-yl)methyl, R3=Trifluoromethyl) (22 mg, 41%) as an off-white solid; LC/MS, method 2, Rt=2.59 min, MS m/z 552 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.90 (s, 1H), 7.85-7.76 (m, 2H), 7.62 (s, 1H), 7.45-7.37 (m, 2H), 5.98 (s, 1H), 3.65 (q, J=14.6 Hz, 2H), 3.41-3.32 (m, 1H), 3.14-2.99 (m, 2H), 2.96-2.86 (m, 1H), 2.36-2.25 (m, 1H), 2.20-2.08 (m, 1H), 2.08-1.55 (m, 12H), 1.49-1.35 (m, 1H). (Example 75)
