4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]benzonitrile → 1-{4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]phenyl}methanamine

HRID 12967Notes

Reaction equation

HRID 12967 reaction equation
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1>N.CO.[Ni]>[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:17]=[CH:16][C:13]([CH2:14][NH2:15])=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1

Participants

5

Reactant 1

HCID 247437814-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]benzonitrile

Product 1

HCID 247437821-{4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]phenyl}methanamine

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

The product of Example 68 (676 mg, 3.0 mmole) in 50 mL of 20% ammonia in methanol was stirred in the presence of 6.8 g Raney-Nickel under an atmosphere of hydrogen at 60 psi at room temperature for 4 hours. Catalyst was removed by filtration through CELITE® and the filtrate concentrated under reduced pressure. The resulting oil was purified by flash chromatography (eluting with a mixture of 5% basic methanol in dichloromethane) to provide the titled compound. 1H NMR (CDCl3) δ ppm 7.17 (d, J=8.82 Hz, 2H) 6.55 (d, J=8.48 Hz, 2H) 4.07-4.16 (m, 1H) 3.77 (s, 2H) 3.45-3.59 (m, 1H) 3.16-3.28 (m, 1H) 2.88-3.04 (m, 1H) 2.63-2.74 (m, 2H) 2.53-2.63 (m, 2H) 2.34 (s, 3H) 2.08-2.23 (m, 1H) 1.86-2.05 (m, 1H); MS (M+H)+=232.

Workup

  1. customCatalyst was removed by filtration through CELITE®
  2. concentrationthe filtrate concentrated under reduced pressure
  3. customThe resulting oil was purified by flash chromatography (
  4. washeluting with a mixture of 5% basic methanol in dichloromethane)

Sources & evidence

ORD record
ord-503c3097b53d4b15a86fbc4038f5e105
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Reaction notes

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