HCID 59618815, compound → HCID 59618712, compound

HRID 1691463Notes

Reaction equation

HRID 1691463 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([C:25](=[O:27])[CH3:26])[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:28]=[C:29]([C:32]([F:35])([F:34])[F:33])[CH:30]=[CH:31][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([CH:25]([OH:27])[CH3:26])[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:28]=[C:29]([C:32]([F:34])([F:35])[F:33])[CH:30]=[CH:31][C:16]=3[CH2:15]2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 59618815HCID 59618815, compound

Product 1

HCID 59618712HCID 59618712, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]ethanone (Example 454, 100 mg, 0.200 mmol) in THF (0.50 mL) was added borane-THF complex (0.700 mL of 1M solution). After stirring at rt for 2 h, the reaction mixture was cooled to 0° C. and was quenched with 3N HCl, and the stirring continued at rt for 1 h. The product was extracted into EtOAc, and the combined extracts were washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 column chromatography, eluting with mixtures of EtOAc in hexane, to provide title compound as a racemic mixture. LC/MS: m/e 506.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.59 (1H, d, J=1.9 Hz), 7.56 (1H, d, J=7.3 Hz), 7.35 (1H, dd, J=8.4, 2.0 Hz), 7.12 (21-1, d, J=8.4 Hz), 7.05 (1H, d, J=7.5 Hz), 6.96 (2H, d, J=8.5 Hz), 6.85 (1H, s), 6.74 (1H, d, J=8.3 Hz), 4.95 (1H, q, J=6.4 Hz), 4.80 (1H, br s), 1.57 (3H, d, J=6.7 Hz), 1.26 (9H, s). The racemic mixture was separated into its enantiomers eluting on a Chiracel AD-H column (isocratic 15% EtOH in hexanes, 8 mL/min, 254 nM) with retention time of 22 min and 33 min, respectively. Faster enantiomer E1: LC/MS: m/e 506.0 (M+H)+. Slower enantiomer E2: LC/MS: m/e 506.0 (M+H).

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. customwas quenched with 3N HCl
  3. waitthe stirring continued at rt for 1 h
  4. extractionThe product was extracted into EtOAc
  5. washthe combined extracts were washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by SiO2 column chromatography
  9. washeluting with mixtures of EtOAc in hexane

Sources & evidence

ORD record
ord-781945820aa245f9a7013553976327ab
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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