HCID 86722327, compound → HCID 86722328, compound

HRID 718752Notes

Reaction equation

HRID 718752 reaction equation
[CH2:1]([C:3]12[CH2:27][CH2:26][C:25](=[O:28])[CH:24]=[C:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[C:10]3[C:14](=[CH:15][C:16]=12)[CH:13]=[N:12][N:11]3[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH3:2]>C1(C)C=CC=CC=1.[OH-].[OH-].[Pd+2]>[CH2:1]([C@:3]12[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][C@@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[C:10]3[C:14](=[CH:15][C:16]=12)[CH:13]=[N:12][N:11]3[C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1)[CH3:2].[CH2:1]([C@@:3]12[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[C:10]3[C:14](=[CH:15][C:16]=12)[CH:13]=[N:12][N:11]3[C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1)[CH3:2]

Participants

4

Reactant 1

HCID 86722327HCID 86722327, compound

Product 1

HCID 86722328HCID 86722328, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 1140TolueneSolvent

Procedure

A solution of (12b-ethyl-9-(4-fluorophenyl)-1,2,6,7,9,12b-hexahydro-5H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (8, R1=4-Fluorophenyl, R2=Ethyl) (3.03 g, 8.09 mmol) in toluene (75 mL) containing 20% Pd(OH)2 on carbon (0.290 g, 0.413 mmol) was evacuated and placed under hydrogen. The reaction was shaken under about 55 psi of hydrogen for about 12 h then at about 55° C. for about 6 h. The catalyst was removed by filtration through Celite® and the filtrate was concentrated under reduced pressure. The residue was treated with EtOAc (20 mL) and the solids which formed upon standing were collected by filtration and washed with EtOAc (3 mL). The filtrate was retained. The solid was recrystallized from EtOAc (25 mL) to yield (4aR,12bR)-12b-ethyl-9-(4-fluorophenyl)-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one; compound with (4aS,12bS)-12b-ethyl-9-(4-fluoro-phenyl)-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (10, R1=4-Fluorophenyl, R2=Ethyl) (1.26 g, 41%); LC/MS, method 2, Rt=3.05 min, MS m/z 377 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.27 (d, J=0.8 Hz, 1H), 7.86 (s, 1H), 7.83-7.77 (m, 2H), 7.59 (s, 1H), 7.45-7.37 (m, 2H), 3.29-3.24 (m, 1H), 2.99-2.94 (m, 1H), 2.55-2.43 (m, 3H), 2.40-2.11 (m, 3H), 2.09-1.85 (m, 5H), 1.64-1.57 (m, 1H), 1.37-1.28 (m, 1H), 0.49 (t, J=7.3 Hz, 3H).

Workup

  1. customwas evacuated
  2. waitat about 55° C. for about 6 h
  3. customThe catalyst was removed by filtration through Celite®
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionThe residue was treated with EtOAc (20 mL)
  6. customthe solids which formed
  7. filtrationupon standing were collected by filtration
  8. washwashed with EtOAc (3 mL)
  9. customThe solid was recrystallized from EtOAc (25 mL)

Sources & evidence

ORD record
ord-555807ce412c4d41a623d062aa798b85
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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