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

HRID 586893노트

반응식

HRID 586893 반응식
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]([CH2:29][CH3:30])[CH2:27][CH2:26][C:25]([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:24][C:23]=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>[CH2:29]([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:49][C:23]=2[CH:24]=[C:25]([C:31]([NH:33][C:34]2[CH:35]=[CH:36][C:37]([CH2:40][N:41]([CH3:48])[CH:42]3[CH2:43][CH2:44][O:45][CH2:46][CH2:47]3)=[CH:38][CH:39]=2)=[O:32])[CH2:26][CH2:27]1)[CH3:30]

참가 물질

7

반응물 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 867568144-(2-Propoxyethoxy)phenyl borate

생성물 1

HCID 30094061-ethyl-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide수율 46%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매HCID 86587398Ethanol toluene water용매

실험 절차

In a mixture of water:ethanol:toluene (1:1:10, v/v, 18.0 ml) were dissolved 4-(2-propoxyethoxy)phenyl borate (272 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 (404 mg). To the solution was added potassium carbonate (269 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (37 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 (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 1-ethyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 17) (221 mg, 46%) as yellow crystals.

후처리

  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 (30 g, ethyl acetate→ethyl acetate:ethanol=10:1→ethyl acetate:ethanol:triethylamine=100:10:0.5)
  7. customrecrystallized from ethyl acetate/IPE

출처 및 근거

ORD 기록
ord-c9ba718b6f9a47319322487fa4b85e92
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06936602B1

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