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

HRID 586889Notes

Reaction equation

HRID 586889 reaction equation
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH3:15])=[CH:5][CH:4]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[N:28]([CH3:29])[CH2:27][CH2:26][C:25]([C:30]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([CH2:39][N:40]([CH3:47])[CH:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[CH:35][CH:34]=3)=[O:31])=[CH:24][C:23]=2[CH:48]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C.C1(C)C=CC=CC=1.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>[CH3:29][N:28]1[C:22]2[CH:21]=[CH:20][C:19]([C:3]3[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH3:15])=[CH:5][CH:4]=3)=[CH:48][C:23]=2[CH:24]=[C:25]([C:30]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([CH2:39][N:40]([CH3:47])[CH:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[CH:37][CH:38]=2)=[O:31])[CH2:26][CH2:27]1

Participants

7

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 867568144-(2-Propoxyethoxy)phenyl borate

Product 1

HCID 30094021-methyl-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideYield 35.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

In a mixture of water:ethanol:toluene (1:1:10, v/v, 18.0 ml) were dissolved 4-(2-propoxyethoxy)phenyl borate (242 mg) and 7-bromo-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (436 mg). To the solution was added potassium carbonate (299 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (42 mg), and the mixture was heated to reflux under argon atmosphere for 10 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, 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 (30 g, ethyl acetate:ethanol:triethylamine=180:20:1) and recrystallized from ethanol/hexane to give 1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-benzazepine-4-carboxamide (Compound 12) (186 mg, 35%) as yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under argon atmosphere for 10 hours
  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 (30 g, ethyl acetate:ethanol:triethylamine=180:20:1)
  7. customrecrystallized from ethanol/hexane

Sources & evidence

ORD record
ord-552426c7b5424be4aa6169410162176a
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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