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

HRID 586902Notes

Reaction equation

HRID 586902 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][CH2:15][CH3:16])=[CH:5][CH:4]=1.Br[C:20]1[CH:21]=[CH:22][C:23]2[N:29]([CH2:30][CH2:31][CH3:32])[CH2:28][CH2:27][C:26]([C:33]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([CH2:42][N:43]([CH3:50])[CH:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[CH:38][CH:37]=3)=[O:34])=[CH:25][C:24]=2[CH:51]=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>[CH2:13]([O:12][CH2:11][CH2:10][O:9][C:6]1[CH:7]=[CH:8][C:3]([C:20]2[CH:21]=[CH:22][C:23]3[N:29]([CH2:30][CH2:31][CH3:32])[CH2:28][CH2:27][C:26]([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH2:42][N:43]([CH3:50])[CH:44]5[CH2:45][CH2:46][O:47][CH2:48][CH2:49]5)=[CH:40][CH:41]=4)=[O:34])=[CH:25][C:24]=3[CH:51]=2)=[CH:4][CH:5]=1)[CH2:14][CH2:15][CH3:16]

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 867568154-Butoxyethoxyphenyl borate

Product 1

HCID 30094087-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideYield 50%

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, 24.0 ml) were dissolved 4-(2-butoxyethoxy)phenyl borate (519 mg) and 7-bromo-1-propyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (745 mg). To the solution was added potassium carbonate (482 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (67 mg), and the mixture was refluxed 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 (35 g, ethyl acetate→ethyl acetate:ethanol=10:1) and recrystallized from ethyl acetate-IPE to give 7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1-propyl-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 27) (453 mg, 50%) as yellow crystals.

Workup

  1. temperaturethe mixture was refluxed under argon atmosphere for 10 hours
  2. washwashed with water and saturated brine
  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 (35 g, ethyl acetate→ethyl acetate:ethanol=10:1)
  6. customrecrystallized from ethyl acetate-IPE

Sources & evidence

ORD record
ord-1663acb8189d47acadb1855f0eb87e4f
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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