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 586892ノート

反応式

HRID 586892 の反応式
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]

参加物

7

反応物 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

生成物 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-carboxamide収率 53%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 86587398Ethanol toluene water溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-23c06457659d444089e54a08c50a6e76
出典データセット
uspto-grants-2005_08
特許番号
US06936602B1

反応ノート

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