Potassium Carbonate → N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1-propyl-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 587094Notes

Reaction equation

HRID 587094 reaction equation
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[N:27]([CH2:28][CH2:29][CH3:30])[CH2:26][CH2:25][C:24]([C:31]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([CH2:40][N:41]([CH3:48])[CH:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[CH:36][CH:35]=3)=[O:32])=[CH:23][C:22]=2[CH:49]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:48][N:41]([CH2:40][C:37]1[CH:36]=[CH:35][C:34]([NH:33][C:31]([C:24]2[CH2:25][CH2:26][N:27]([CH2:28][CH2:29][CH3:30])[C:21]3[CH:20]=[CH:19][C:18]([C:3]4[CH:8]=[CH:7][C:6]([N:9]5[CH2:14][CH2:13][O:12][CH2:11][CH2:10]5)=[CH:5][CH:4]=4)=[CH:49][C:22]=3[CH:23]=2)=[O:32])=[CH:39][CH:38]=1)[CH:42]1[CH2:43][CH2:44][O:45][CH2:46][CH2:47]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 223289007-bromo-1-propyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideHCID 867561794-Morpholinophenyl borate

Product 1

HCID 22329104N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1-propyl-2,3-dihydro-1-benzazepine-4-carboxamideYield 48.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-morpholinophenyl borate (237 mg) and 7-bromo-1-propyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (391 mg) were dissolved in water:ethanol toluene (=1:1:10, v/v, 18.0 ml), and potassium carbonate (253 mg) was added thereto. This mixture was stirred at room temperature for 30 minutes under argon atmosphere, tetrakistriphenylphosphinepalladium (35 mg) was added thereto, and the mixture was heated to reflux for 10 hours under argon atmosphere. The reaction mixture was diluted with ethyl acetate, and washed with water and saturated brine. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate→ethyl acetate:ethanol=10:1), which was further recrystallized from ethyl acetate-diisopropyl ether-hexane to give N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1-propyl-2,3-dihydro-1-benzazepine-4-carboxamide (222 mg) as yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 10 hours under argon atmosphere
  3. washwashed with water and saturated brine
  4. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified with silica gel column chromatography (ethyl acetate→ethyl acetate:ethanol=10:1), which
  7. customwas further recrystallized from ethyl acetate-diisopropyl ether-hexane

Sources & evidence

ORD record
ord-9f66748f92fc40959c21e7989fd592df
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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