Rac-9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile → (2S,7R)-14-(4-fluorophenyl)-5-oxo-14,15-diazatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),12,15,17-tetraene-2-carbonitrile;(2R,7S)-14-(4-fluorophenyl)-5-oxo-14,15-diazatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),12,15,17-tetraene-2-carbonitrile

HRID 718773Notes

Reaction equation

HRID 718773 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20]5[C:21]([C:27]#[N:28])([CH2:22][CH2:23][C:24](=[O:26])[CH:25]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[H][H]>C1(C)C=CC=CC=1.O[Pd]O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@H:20]5[CH2:25][C:24](=[O:26])[CH2:23][CH2:22][C@:21]5([C:27]#[N:28])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@@H:20]5[CH2:25][C:24](=[O:26])[CH2:23][CH2:22][C@@:21]5([C:27]#[N:28])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 86722360Rac-9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 86722357(2S,7R)-14-(4-fluorophenyl)-5-oxo-14,15-diazatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),12,15,17-tetraene-2-carbonitrile;(2R,7S)-14-(4-fluorophenyl)-5-oxo-14,15-diazatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),12,15,17-tetraene-2-carbonitrileYield 72%

Reagents, catalysts & solvents 2

HCID 178526213HCID 178526213, compoundCatalystHCID 1140TolueneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6f27fd703bc34f1eb8ab36ee0668dd2f
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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