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 566126ノート

反応式

HRID 566126 の反応式
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

参加物

6

反応物 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

生成物 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-carboxamide収率 19.2%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 86587398Ethanol toluene water溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-22bc36a975534e75874cc94d127a4799
出典データセット
uspto-grants-2001_01
特許番号
US06172061B2

反応ノート

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