Acetone → 4'-[(3aR,6aR)-5-isopropylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]-1,1'-biphenyl-4-carbonitrile

HRID 1947383Notes

Reaction equation

HRID 1947383 reaction equation
[N:1]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4][C@@H:3]2[CH2:6][NH:7][CH2:8][C@H:2]12.[CH3:23][C:24]([CH3:26])=O.C([BH3-])#N.[Na+]>CO.[OH-].[Na+]>[CH:24]([N:7]1[CH2:6][C@@H:3]2[C@@H:2]([N:1]([C:9]3[CH:10]=[CH:11][C:12]([C:15]4[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=4)=[CH:13][CH:14]=3)[CH2:5][CH2:4]2)[CH2:8]1)([CH3:26])[CH3:23]

Participants

6

Reactant 3

HCID 180AcetoneHCID 5003444Sodium cyanoborohydrideHCID 44221502(3aR,6aR)-4'-(Hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile

Product 1

HCID 247439884'-[(3aR,6aR)-5-isopropylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]-1,1'-biphenyl-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of the product of Example 1E (26 mg, 0.09 mmole) in methanol (2 ml) was added acetone (132 μl, 1.8 mmole), and the mixture was stirred at room temperature for 1.5 hour. Sodium cyanoborohydride (28 mg, 0.44 mmole) was added and the mixture stirred overnight. The mixture was diluted with 2 ml 1N NaOH and extracted with dichloromethane (with 5% methanol) (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluting with a mixture of 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane) to provide the title compound. 1H NMR (CDCl3) δ ppm 7.63 (d, J=3.74 Hz, 4H) 7.50 (d, J=9.05 Hz, 2H) 6.64 (d, J=8.73 Hz, 2H) 4.16-4.22 (m, 1H) 3.48-3.55 (m, 1H) 3.31-3.38 (m, 1H) 2.90-3.01 (m, 2H) 2.74 (t, J=7.96 Hz, 1H) 2.46-2.52 (m, 2H) 2.31-2.39 (m, 1H) 2.10-2.20 (m, 1H) 1.90-1.99 (m, 1H) 1.06 (dd, J=6.24, 1.87 Hz, 6H); MS (M+H)+=332.

Workup

  1. stirringthe mixture stirred overnight
  2. extractionextracted with dichloromethane (with 5% methanol) (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (
  8. washeluting with a mixture of 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c783da22e30846ffb32c0e9bd901bd97
Source dataset
uspto-grants-2013_03
Patent number
US08399468B2

Reaction notes

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