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

HRID 1978702ノート

反応式

HRID 1978702 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.C1(C)C=CC=CC=1.C(O)C.O.B([O-])([O-])O[C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][CH3:59])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>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.O>[CH3:31][N:24]([CH2:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:8]2[CH2:9][CH2:10][S:11](=[O:13])(=[O:12])[C:5]3[CH:4]=[CH:3][C:2]([C:46]4[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][CH3:59])=[CH:48][CH:47]=4)=[CH:32][C:6]=3[CH:7]=2)=[O:15])=[CH:18][CH:19]=1)[CH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideHCID 86587398Ethanol toluene waterHCID 867568184-(3-Propoxypropoxy)phenyl borate

生成物 1

HCID 21995790N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxypropoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide収率 67%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

実験手順

To 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (300 mg) were added toluene/ethanol/water (10/1/1, 19.2 ml) and then were added 4-(3-propoxypropoxy)phenyl borate (165 mg) and potassium carbonate (175 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (27 mg), and the mixture was refluxed for 14 hours and cooled to room temperature. The mixture was added to water, and the mixture was extracted with ethyl acetate/THF, washed with, saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1) and recrystallized from ethanol to give N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxypropoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 103) (245 mg).

後処理

  1. temperaturethe mixture was refluxed for 14 hours
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted with ethyl acetate/THF
  4. washwashed with, saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customUnder reduced pressure, the solvent was evaporated
  7. customthe residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1)
  8. customrecrystallized from ethanol

出典と根拠

ORDレコード
ord-26018b43637e4de5843734366e632b14
出典データセット
uspto-grants-2001_05
特許番号
US06235771B1

反応ノート

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