Methanol → HCID 66901654, compound

HRID 1691433Notes

Reaction equation

HRID 1691433 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.C(N(CC)CC)C.[CH3:41][OH:42].[C]=O.CN([CH:48]=[O:49])C>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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:41]([O:49][CH3:48])=[O:42])[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

9

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 596186368-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×HCID 178418416HCID 178418416, compound

Product 1

HCID 66901654HCID 66901654, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (0.168 g, 0.32 mmol, intermediate 53) in DMF (2.0 mL) under nitrogent (balloon) was added palladium acetate (0.072 g, 0.32 mmol), dppf (0.220 g, 0.40 mmol), triethylamine (0.080 g, 0.800 mmol), and methanol (2.0 mL). The nitrogen balloon was replaced with a carbon monoxide balloon and the reaction mixture was stirred at rt for 1 h, and at 80° C. for 15 h. After cooling to rt, the reaction mixture was diluted with EtOAc and filtered through a pad of silica gel. The filtrate was concentrated to dryness and the residue was purified by SiO2 column chromatography eluting with EtOAc in hexanes to provide the title compound. LC/MS: m/e 520.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 8.28 (1H, d, J=1.6 Hz), 7.94 (1H, dd, J=8.5, 1.8 Hz), 7.61 (1H, d, J=7.5 Hz), 7.13 (1H, d, J=7.6 Hz), 7.10 (2H, d, J=8.5 Hz), 6.99 (1H, s), 6.92 (2H, d, J=8.4 Hz), 6.80 (1H, m), 4.70-4.90 (2H, br), 3.95 (3H, s), 1.25 (9H, s).

Workup

  1. waitat 80° C. for 15 h
  2. temperatureAfter cooling to rt
  3. filtrationfiltered through a pad of silica gel
  4. concentrationThe filtrate was concentrated to dryness
  5. customthe residue was purified by SiO2 column chromatography
  6. washeluting with EtOAc in hexanes

Sources & evidence

ORD record
ord-cec5c9dffd584e66a417aba83d17a1f8
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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