反应详情

A solution of 9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (30, R1=4-Fluorophenyl) (28.0 g, 67.9 mmol) in toluene (600 mL) containing dihydroxypalladium (4.29 g, 3.05 mmol) was hydrogenated on a Parr shaker at about 55° C. and about 50 psi of hydrogen for about 10 h. The reaction was cooled to rt and filtered (Celite®), rinsing with DCM (3×200 mL). The combined organics were concentrated to about 100 mL, the product was filtered off and dried under reduced pressure to yield (4aR,12bS)-9-(4-fluorophenyl)-3-oxo-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile; compound with (4aS,12bR)-9-(4-fluorophenyl)-3-oxo-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (31, R1=4-Fluorophenyl) (18.2 g, 72%) as an off-white solid. LC/MS, method 3, Rt=2.41 min, MS m/z 374 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 8.06 (s, 1H), 7.85-7.79 (m, 2H), 7.71 (s, 1H), 7.47-7.40 (m, 2H), 3.47-3.36 (m, 1H), 3.15-3.04 (m, 1H), 2.93-2.63 (m, 4H), 2.44-2.30 (m, 2H), 2.26-2.14 (m, 1H), 2.10-1.99 (m, 1H), 1.95-1.84 (m, 2H), 1.40-1.27 (m, 1H).

1. customwas hydrogenated on a Parr shaker at about 55° C.
2. filtrationfiltered (Celite®)
3. washrinsing with DCM (3×200 mL)
4. concentrationThe combined organics were concentrated to about 100 mL
5. filtrationthe product was filtered off
6. customdried under reduced pressure