Potassium Carbonate → 1-formyl-7-(4-methylphenyl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 2228313Notes

Reaction equation

HRID 2228313 reaction equation
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1.Br[C:13]1[CH:14]=[CH:15][C:16]2[N:22]([CH:23]=[O:24])[CH2:21][CH2:20][C:19]([C:25]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([CH2:34][N:35]([CH3:42])[CH:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:30][CH:29]=3)=[O:26])=[CH:18][C:17]=2[CH:43]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:23]([N:22]1[C:16]2[CH:15]=[CH:14][C:13]([C:3]3[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=3)=[CH:43][C:17]=2[CH:18]=[C:19]([C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:35]([CH3:42])[CH:36]3[CH2:37][CH2:38][O:39][CH2:40][CH2:41]3)=[CH:30][CH:29]=2)=[O:26])[CH2:20][CH2:21]1)=[O:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 22329057HCID 22329057, compoundHCID 866453334-Methylphenyl borate

Product 1

HCID 184726701-formyl-7-(4-methylphenyl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideYield 33%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

In water/ethanol/toluene (1:1:10, 60.0 ml) were dissolved 4-methylphenyl borate (658 mg) and 7-bromo-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4- carboxamide (2.01 g), and to the mixture was added potassium carbonate (1.34 g). Under argon atmosphere, the mixture was stirred for 30 minutes, and to the mixture was added tetrakistriphenylphosphine palladium(186 mg). Under argon atmosphere, the mixture was refluxed for 17 hours, and the mixture was dilute with ethyl acetate (750 ml). The mixture was washed with water (200 ml) and saturated brine (100 ml), and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (150 g, ethyl acetate→ethyl acetate/ethanol=20:1) and recrystallized from ethanol to give 1-formyl-7-(4-methylphenyl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 317) (669 mg, 33%).

Workup

  1. temperatureUnder argon atmosphere, the mixture was refluxed for 17 hours
  2. washThe mixture was washed with water (200 ml) and saturated brine (100 ml)
  3. dry with materialthe organic layer was dried with anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified with silica gel column chromatography (150 g, ethyl acetate→ethyl acetate/ethanol=20:1)
  6. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-e2f8e4d59d804dc08c79ba38c0f6c8f9
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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