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

HRID 2228311Notes

Reaction equation

HRID 2228311 reaction equation
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.Br[C:17]1[CH:18]=[CH:19][C:20]2[N:26]([CH3:27])[CH2:25][CH2:24][C:23]([C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([CH2:37][N:38]([CH3:45])[CH:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:33][CH:32]=3)=[O:29])=[CH:22][C:21]=2[CH:46]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:27][N:26]1[C:20]2[CH:19]=[CH:18][C:17]([C:3]3[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=3)=[CH:46][C:21]=2[CH:22]=[C:23]([C:28]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([CH2:37][N:38]([CH3:45])[CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[CH:35][CH:36]=2)=[O:29])[CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 223290367-bromo-1-methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepine-4-carboxamideHCID 867561694-Trifluoromethoxyphenyl borate

Product 1

HCID 184725311-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-(4-trifluoromethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxamideYield 31.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

In water/ethanol/toluene(1:1:10, 18.0 ml) were dissolved 4-trifluoromethoxyphenyl borate (208 mg) and 7-bromo-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (407 mg), and to the mixture was added potassium carbonate (279 mg). Under argon atmosphere, the mixture was stirred for 30 minutes, and the mixture was added tetrakistriphenylphosphine palladium (39 mg). Under argon atmosphere, the mixture was refluxed for 16 hours, and the mixture was diluted with ethyl acetate (200 ml). The mixture was washed with water (50 ml) and saturated brine (50 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 (75 g, ethyl acetate→ethyl acetate/ethanol=20:1) and recrystallized from ethanol to give 1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-(4-trifluoromethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 315) (148 mg, 31%).

Workup

  1. temperatureUnder argon atmosphere, the mixture was refluxed for 16 hours
  2. washThe mixture was washed with water (50 ml) and saturated brine (50 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
  6. customcolumn chromatography (75 g, ethyl acetate→ethyl acetate/ethanol=20:1) and recrystallized from ethanol

Sources & evidence

ORD record
ord-49d779b696994f18899f79051ae6a2da
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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