N-methyl-2-pyrrolidone → 6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbonitrile

HRID 1691431Notes

Reaction equation

HRID 1691431 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:33]=1.[CH3:34][N:35]1C(=O)CCC1>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:29]([C:26]1[CH:27]=[CH:28][C:23]([S:20]([N:7]2[C:6]3[CH:33]=[C:2]([C:34]#[N:35])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:22])=[O:21])=[CH:24][CH:25]=1)([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 596186368-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×

Product 1

HCID 669015676-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (0.860 g, 1.60 mmol, intermediate 53), zinc cyanide (0.112 g, 0.96 mmol), Pd2(dba)3 (0.293 g, 0.320 mmol), and dppf (0.443 g, 0.80 mmol) in NMP (6.5 mL) under nitrogen was stirred at rt for 0.5 h and at 100° C. overnight. After cooling to rt, the reaction mixture was diluted with EtOAc and filtered. The filtrate was washed with water (3×), brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography, eluting with mixtures of hexane and EtOAc, to provide the title compound. LC/MS: m/e 487.2 (M+H)+. NMR (500 MHz, CDCl3): δ 7.94 (1H, d, J=1.6 Hz), 7.66 (1H, d, J=7.5 Hz), 7.53 (1H, dd, J=8.4, 2.0 Hz), 7.19 (1H, d, J=7.3 Hz), 7.13 (2H, d, J=8.7 Hz), 7.04 (1H, s), 6.94 (2H, d, J=8.6 Hz), 6.83 (1H, d, J=8.5 Hz), 4.70-4.90 (2H, br), 1.26 (9H, s).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationfiltered
  3. washThe filtrate was washed with water (3×), brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with mixtures of hexane and EtOAc

Sources & evidence

ORD record
ord-55838610b2454205a139f7f8d0605236
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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