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

HRID 2228312노트

반응식

HRID 2228312 반응식
B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[N:27]([CH3:28])[CH2:26][CH2:25][C:24]([C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([CH2:38][N:39]([CH3:46])[CH:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)=[CH:34][CH:33]=3)=[O:30])=[CH:23][C:22]=2[CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:28][N:27]1[C:21]2[CH:20]=[CH:19][C:18]([C:3]3[CH:8]=[CH:7][C:6]([N:9]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:5][CH:4]=3)=[CH:47][C:22]=2[CH:23]=[C:24]([C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([CH2:38][N:39]([CH3:46])[CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:36][CH:37]=2)=[O:30])[CH2:25][CH2:26]1

참가 물질

6

반응물 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 867561844-Piperidinophenyl borate

생성물 1

HCID 212680281-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]-phenyl]-7-[4-(1-piperidinyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide수율 19.2%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 86587398Ethanol toluene water용매

실험 절차

In water/ethanol/toluene (1:1:10, 18.0 ml) were dissolved 4-(1-piperidinyl)phenyl borate (179 mg) and 7-bromo-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (353 mg), and to the mixture was added potassium carbonate (242 mg). Under argon atmosphere, the mixture was stirred for 40 minutes, and to the mixture was added tetrakistriphenylphosphine palladium (34 mg). Under argon atmosphere, the mixture was refluxed for 15 hours, and the mixture was dilute with ethyl acetate (200 ml). The mixture was washed with water (50 ml) and saturated brine (50 ml), 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 (75 g, ethyl acetate/ethanol=9:1) and recrystallized from ethanol to give 1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]-phenyl]-7-[4- (1-piperidinyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 316) (79 mg, 19%).

후처리

  1. temperatureUnder argon atmosphere, the mixture was refluxed for 15 hours
  2. washThe mixture was washed with water (50 ml) and saturated brine (50 ml)
  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 (75 g, ethyl acetate/ethanol=9:1)
  6. customrecrystallized from ethanol

출처 및 근거

ORD 기록
ord-fabbfdf05df843428af327155d73ee30
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06413947B1

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