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

HRID 12949Notes

Reaction equation

HRID 12949 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 (elating 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. additionelating with a mixture of 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-81e7eec0ca60446faf758efa1432470c
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Reaction notes

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