HCID 86722469, compound → HCID 86722468, compound

HRID 718855Notes

Reaction equation

HRID 718855 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20]5[C:21]([CH2:27][C:28]6[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=6)([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]>C1COCC1.N1C=CC=CC=1.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][CH:20]5[CH2:25][C:24](=[O:26])[CH2:23][CH2:22][C:21]5([CH2:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 86722469HCID 86722469, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86722468HCID 86722468, compoundYield 59.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

9-(4-Fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,5,6,7,9,12b-hexahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3 (2H)-one (116, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (9.28 g, 21.16 mmol) in THF (170 mL) and pyridine (22 mL) with palladium on carbon (10%) (0.690 g, 0.648 mmol) was hydrogenated in a Parr shaker at 50 psi hydrogen and rt for about 8 h. The mixture was filtered through a pad of Celite® and the pad was washed with DCM. The filtrate was concentrated under reduced pressure and the material was purified on silica gel (330 g) using a gradient from 0-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-(4aR,12bR)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3(2H)-one (118, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (5.55 g, 59.5%); LC/MS, method 3, Rt=2.46 min, MS m/z 441 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.40-8.37 (m, 2H), 8.31-8.29 (m, 1H), 8.19 (s, 1H), 7.80 (s, 1H), 7.47-7.38 (m, 3H), 7.09-7.05 (m, 1H), 6.61 (d, J=7.8 Hz, 1H), 3.83 (d, J=12.9 Hz, 1H), 3.63-3.56 (m, 1H), 3.40-3.35 (m, 1H), 2.97 (d, J=13.0 Hz, 1H), 2.62-1.81 (m, 9H), 1.75-1.65 (m, 2H).

Workup

  1. filtrationThe mixture was filtered through a pad of Celite®
  2. washthe pad was washed with DCM
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe material was purified on silica gel (330 g)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5073580c724c4f8c8b4776f7f66ec07a
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…