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

HRID 2228316Notes

Reaction equation

HRID 2228316 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[CH2:10][CH2:9][C:8]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:30])[CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:18][CH:17]=3)=[O:14])=[CH:7][C:6]=2[CH:31]=1.C(=O)([O-])[O-].[K+].[K+].B([O-])([O-])O[C:40]1[CH:45]=[CH:44][C:43]([S:46][CH2:47][CH3:48])=[CH:42][CH:41]=1>O.C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:47]([S:46][C:43]1[CH:44]=[CH:45][C:40]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH3:12])[CH2:10][CH2:9][C:8]([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:30])[CH:24]5[CH2:25][CH2:26][O:27][CH2:28][CH2:29]5)=[CH:18][CH:17]=4)=[O:14])=[CH:7][C:6]=3[CH:31]=2)=[CH:41][CH:42]=1)[CH3:48]

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 1317222494-Ethylthiophenyl borate

Product 1

HCID 184724297-(4-ethylthiophenyl)-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideYield 34%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

In water/ethanol/toluene (1:1:10, 18.0 ml) were dissolved 4-ethylthiophenyl borate.(264 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 (439 mg), and to the mixture was added potassium carbonate (301 mg). Under argon atmosphere, the mixture was stirred for 30 minutes, and to the mixture was added tetrakistriphenylphosphine palladium (42 mg). Under argon atmosphere, the mixture was refluxed for 17.5 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 ethyl acetate/ethanol=9:1) and recrystallized from ethanol to give 7-(4-ethylthiophenyl)-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 320) (168 mg, 34%).

Workup

  1. temperatureUnder argon atmosphere, the mixture was refluxed for 17.5 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 ethyl acetate/ethanol=9:1)
  6. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-6c44a1b5b0dd461ab169b9bd10b9ac20
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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