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 1691431노트

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HRID 1691431 반응식
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]

참가 물질

7

반응물 2

HCID 13387N-methyl-2-pyrrolidoneHCID 59618636HCID 59618636, 화합물2회

생성물 1

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

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-55838610b2454205a139f7f8d0605236
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08153626B2

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