Reaction Steps
Ethynylmagnesium bromide (0.5 M solution in THF, 6.00 mL, 3.00 mmol) was added dropwise over about 15 min to a mixture of (4aR,12bR)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-3 (2H)-one; compound with (4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (9, R1=4-Fluorophenyl, R2=Ethyl) (0.200 g, 0.531 mmol) and THF (2.5 mL) under a nitrogen atmosphere at about 0° C. After about 90 min, the ice bath was removed and the solution was stirred at rt for about 1 h. Sat. aq. NH4Cl (10 mL) and water (10 mL) were added. The solution was extracted with DCM (2×20 mL). The combined organics were dried over Na2SO4 and filtered. Silica gel (2 g) was added and the organic volatiles were removed under reduced pressure. The resulting solid was purified on silica gel (12 g) using a gradient of 0-3% EtOAc in DCM. The fractions containing product were combined and concentrated under reduced pressure to afford (3R,4aR,12bR)-12b-ethyl-3-ethynyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol; compound with (3S,4aS,12bS)-12b-ethyl-3-ethynyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Ethynyl) (0.116 g, 54% yield). LC/MS, method 2, Rt=2.78 min, MS m/z 403 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.26 (d, J=0.7 Hz, 1H), 7.91 (s, 1H), 7.83-7.76 (m, 2H), 7.55 (s, 1H), 7.45-7.36 (m, 2H), 5.48 (s, 1H), 3.24 (s, 1H), 3.22-3.11 (m, 1H), 2.98-2.88 (m, 1H), 2.32-2.23 (m, 1H), 2.20-1.48 (m, 11H), 1.41-1.26 (m, 1H), 0.37 (t, J=7.3 Hz, 3H).
