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

HRID 586892Notes

Reaction equation

HRID 586892 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][CH3:14])=[CH:5][CH:4]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[N:27]([CH2:28][CH3:29])[CH2:26][CH2:25][C:24]([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:23][C:22]=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>[CH2:13]([O:12][CH2:11][CH2:10][O:9][C:6]1[CH:7]=[CH:8][C:3]([C:18]2[CH:19]=[CH:20][C:21]3[N:27]([CH2:28][CH3:29])[CH2:26][CH2:25][C:24]([C:30]([NH:32][C:33]4[CH:34]=[CH:35][C:36]([CH2:39][N:40]([CH3:47])[CH:41]5[CH2:46][CH2:45][O:44][CH2:43][CH2:42]5)=[CH:37][CH:38]=4)=[O:31])=[CH:23][C:22]=3[CH:48]=2)=[CH:4][CH:5]=1)[CH3:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 223292947-bromo-1-ethyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideHCID 867568084-(2-Ethoxyethoxy)phenyl borate

Product 1

HCID 99600217-[4-(2-ethoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideYield 53%

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-ethoxyethoxy)phenyl borate (339 mg) and 7-bromo-1-ethyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (537 mg). To the solution was added potassium carbonate (357 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (50 mg), and the mixture was heated to reflux under argon atmosphere for 14 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→ethyl acetate:ethanol triethylamine=100:10:0.5) and recrystallized from ethyl acetate/IPE to give 7-[4-(2-ethoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 16) (332 mg, 53%) as yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under argon atmosphere for 14 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 (35 g, ethyl acetate→ethyl acetate ethanol=10:1→ethyl acetate:ethanol triethylamine=100:10:0.5)
  7. customrecrystallized from ethyl acetate/IPE

Sources & evidence

ORD record
ord-23c06457659d444089e54a08c50a6e76
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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