Toluene → HCID 86722452, compound

HRID 718843Notes

Reaction equation

HRID 718843 reaction equation
[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C:18]3([C:28]#[N:29])[CH2:26][CH2:25][C:24](=[O:27])[CH:23]=[C:19]3[CH2:20][CH2:21][O:22][C:3]=12.C1(C)C=CC=CC=1.[H][H]>C(Cl)Cl.[OH-].[OH-].[Pd+2]>[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@@:18]3([C:28]#[N:29])[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][C@@H:19]3[CH2:20][CH2:21][O:22][C:3]=12.[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@:18]3([C:28]#[N:29])[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][C@H:19]3[CH2:20][CH2:21][O:22][C:3]=12

Participants

6

Reactant 3

HCID 1140TolueneHCID 89994526HCID 89994526, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86722452HCID 86722452, compoundYield 45.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 8-bromo-9-(4-fluorophenyl)-3-oxo-2,3,5,6,9,12b-hexahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile (103, R1=4-Fluorophenyl) (2.02 g, 4.47 mmol) and toluene (80 mL) was added to 20% palladium hydroxide on carbon (wet, Deguessa type, 0.314 g). The mixture was shaken under about 50 psi of hydrogen at about 55° C. After about 17 h, the reaction mixture was allowed to cool to rt then filtered through Celite® rinsing with 25% THF/toluene (4×50 mL) then 25% THF/DCM (6×25 mL). The volatiles were removed under reduced pressure to afford a light tan solid which was slurried in DCM (10 mL). The solid was collected by filtration rinsing with DCM (3×10 mL) then dried under reduced pressure to afford (4aR,12bS)-8-bromo-9-(4-fluorophenyl)-3-oxo-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile; compound with (4aS,12bR)-8-bromo-9-(4-fluorophenyl)-3-oxo-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile (104, R1=4-Fluorophenyl) (0.916 g, 45% yield) as an ivory solid. The mother liquor was concentrated under reduced pressure.

Workup

  1. filtrationthen filtered through Celite®
  2. washrinsing with 25% THF/toluene (4×50 mL)
  3. customThe volatiles were removed under reduced pressure
  4. customto afford a light tan solid which
  5. filtrationThe solid was collected by filtration
  6. washrinsing with DCM (3×10 mL)
  7. customthen dried under reduced pressure

Sources & evidence

ORD record
ord-5086b191c57e4ccea566f3db9852c5fc
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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