1-Methyl-4-piperidone → N-(4-{trans-2-[(1-methylpiperidin-4-yl)amino]cyclopropyl}phenyl)-3-(trifluoromethyl)benzamide dihydrochloride

HRID 922537ノート

反応式

HRID 922537 の反応式
[ClH:1].[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)=[CH:8][CH:7]=1.[CH3:25][N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.C(=O)([O-])O.[Na+].[BH4-].[Na+]>CO.C1COCC1>[ClH:1].[ClH:1].[CH3:25][N:26]1[CH2:31][CH2:30][CH:29]([NH:2][C@@H:3]2[CH2:5][C@H:4]2[C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:22])([F:23])[F:21])[CH:15]=3)=[CH:10][CH:11]=2)[CH2:28][CH2:27]1

参加物

7

反応物 4

HCID 740491-Methyl-4-piperidoneHCID 516892Sodium Bicarbonate2 回HCID 4311764Sodium borohydrideHCID 86729839N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride

生成物 1

HCID 86729900N-(4-{trans-2-[(1-methylpiperidin-4-yl)amino]cyclopropyl}phenyl)-3-(trifluoromethyl)benzamide dihydrochloride収率 72.8%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a solution of N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride (80 mg) in methanol (3 mL)/THF (3 mL) were added 1-methylpiperidin-4-one (33.0 mg) and sodium hydrogen carbonate (37.7 mg). The mixture was stirred at 60° C. for 2 hr, and ice-cooled to 0° C. and sodium borohydride (17.0 mg) was added. The mixture was stirred at room temperature for 2 hr, and ice-cooled to 0° C., and saturated aqueous sodium hydrogen carbonate solution was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol). 10% Hydrochloric acid methanol solution was added and the solvent was evaporated under reduced pressure. The residue was recrystallized from methanol/diisopropyl ether to give the title compound (40 mg).

後処理

  1. temperatureice-cooled to 0° C.
  2. stirringThe mixture was stirred at room temperature for 2 hr
  3. temperatureice-cooled to 0° C.
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol)
  9. addition10% Hydrochloric acid methanol solution was added
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was recrystallized from methanol/diisopropyl ether

出典と根拠

ORDレコード
ord-f42407001c464600a6c0363b297bc04a
出典データセット
uspto-grants-2016_03
特許番号
US09278931B2

反応ノート

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