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

HRID 586894Notes

Reaction equation

HRID 586894 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]([CH3:30])[CH2:28][CH2:27][C:26]([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:25][C:24]=2[CH:49]=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]([CH3:30])[CH2:28][CH2:27][C:26]([C:31]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([CH2:40][N:41]([CH3:48])[CH:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[CH:38][CH:39]=4)=[O:32])=[CH:25][C:24]=3[CH:49]=2)=[CH:4][CH:5]=1)[CH2:14][CH2:15][CH3:16]

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 867568154-Butoxyethoxyphenyl borate

Product 1

HCID 30094037-[4-(2-butoxyethoxy)phenyl]-1-methyl-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-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-butoxyethoxy)phenyl borate (324 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 (440 mg). To the solution was added potassium carbonate (301 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 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 (30 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-butoxyethoxy)phenyl]-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 18) (287 mg, 53%) 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 (30 g, ethyl acetate→ethyl acetate:ethanol=10:1→ethyl acetate:ethanol:triethylamine=100:10:0.5)
  6. customrecrystallized from ethyl acetate/IPE

Sources & evidence

ORD record
ord-5ae3283bf78742a0b0c3fb66138fb5f5
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

Loading…