Sodium cyanoborohydride → HCID 44247662, compound

HRID 1969471Notes

Reaction equation

HRID 1969471 reaction equation
[CH3:1][C:2]([NH:14][C:15]1[C:16](=[O:39])[N:17]([C:31]2[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=2)[C@@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)[CH:19]=1)([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[N:5]=1)[CH3:3].C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:3][C:2]([NH:14][C@@H:15]1[CH2:19][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)[N:17]([C:31]2[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=2)[C:16]1=[O:39])([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:11])[F:12])[N:5]=1)[CH3:1]

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 86650670HCID 86650670, compound

Product 1

HCID 44247662HCID 44247662, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Dissolve 4-[(R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-2-oxo-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (1.06 g, 1.94 mmol) in acetic acid (19.4 mL) and add sodium cyanoborohydride (609 mg. 9.70 mmol). Stir 1 hr. at ambient temperature. Concentrate under reduced pressure. Dissolve the residue in dichloromethane and concentrate. Partition the residue between dichloromethane and 5% NaHCO3 solution and extract with dichloromethane. Combine dichloromethane extracts, dry over magnesium sulfate, filter and concentrate under reduced pressure. Purify the residue by silica gel chromatography (25% ethyl acetate-hexane) to obtain 4-[(3R,5R)-3-[1-Methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-2-oxo-5-(3-trifluoromethoxy-phenyl)-pyrrolidin-1-yl]-benzonitrile (751 mg, 71%). 1H NMR (400 MHz, CDCl3) δ 7.80-7.76 (m, 2H), 7.50-7.46 (m, 3H), 7.38 (d, J=8.8 Hz, 2H), 7.29-7.23 (m, 1H), 7.05 (t, J=7.3 Hz, 2H), 6.95 (s, 1H), 4.98 (dd, J=6.2, 9.7 Hz, 1H), 3.46 (dd, J=8.1, 10.8 Hz, 1H), 2.83-2.74 (m, 1H), 1.85-1.76 (m, 1H), 1.54 (d, J=7.0, 6H). LC-MS ESI m/z: 549.0 (M+H)+, Tr=2.285 min., method 2.

Workup

  1. customat ambient temperature
  2. concentrationConcentrate under reduced pressure
  3. dissolutionDissolve the residue in dichloromethane
  4. concentrationconcentrate
  5. customPartition the residue between dichloromethane and 5% NaHCO3 solution
  6. extractionextract with dichloromethane
  7. dry with materialCombine dichloromethane extracts, dry over magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure
  10. customPurify the residue by silica gel chromatography (25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-04188b29f2f54b8990fe089b5178f6e0
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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