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

HRID 2228312Notes

Reaction equation

HRID 2228312 reaction equation
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[N:27]([CH3:28])[CH2:26][CH2:25][C:24]([C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([CH2:38][N:39]([CH3:46])[CH:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)=[CH:34][CH:33]=3)=[O:30])=[CH:23][C:22]=2[CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:28][N:27]1[C:21]2[CH:20]=[CH:19][C:18]([C:3]3[CH:8]=[CH:7][C:6]([N:9]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:5][CH:4]=3)=[CH:47][C:22]=2[CH:23]=[C:24]([C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([CH2:38][N:39]([CH3:46])[CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:36][CH:37]=2)=[O:30])[CH2:25][CH2:26]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 867561844-Piperidinophenyl borate

Product 1

HCID 212680281-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]-phenyl]-7-[4-(1-piperidinyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideYield 19.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

In water/ethanol/toluene (1:1:10, 18.0 ml) were dissolved 4-(1-piperidinyl)phenyl borate (179 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 (353 mg), and to the mixture was added potassium carbonate (242 mg). Under argon atmosphere, the mixture was stirred for 40 minutes, and to the mixture was added tetrakistriphenylphosphine palladium (34 mg). Under argon atmosphere, the mixture was refluxed for 15 hours, and the mixture was dilute 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/ethanol=9:1) and recrystallized from ethanol to give 1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]-phenyl]-7-[4- (1-piperidinyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 316) (79 mg, 19%).

Workup

  1. temperatureUnder argon atmosphere, the mixture was refluxed for 15 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 column chromatography (75 g, ethyl acetate/ethanol=9:1)
  6. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-fabbfdf05df843428af327155d73ee30
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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