Borane;tetrahydrofuran → (R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1771174ノート

反応式

HRID 1771174 の反応式
[Si:1]([O:18][CH2:19][CH2:20][N:21]([CH2:52][CH3:53])[C:22](=O)[CH2:23][C@@H:24]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](=[O:43])(=[O:42])[NH2:41])=[CH:36][C:35]=1[S:44]([C:47]([F:50])([F:49])[F:48])(=[O:46])=[O:45])[CH2:25][S:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.C1COCC1>C1COCC1.N.CO>[Si:1]([O:18][CH2:19][CH2:20][N:21]([CH2:52][CH3:53])[CH2:22][CH2:23][C@@H:24]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH2:41])(=[O:42])=[O:43])=[CH:36][C:35]=1[S:44]([C:47]([F:49])([F:50])[F:48])(=[O:45])=[O:46])[CH2:25][S:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

参加物

6

反応物 2

HCID 2723981Borane;tetrahydrofuran2 回HCID 66723918(R)-N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluorom ethylsulfonyl)phenylamino)butanamide2 回

生成物 1

HCID 66723539(R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide収率 48.3%

試薬・触媒・溶媒 3

HCID 222Ammonia溶媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

(R)—N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanamide (INTERMEDIATE 24, 0.59 g, 0.73 mmol) was dissolved in THF (4.6 ml), under a nitrogen atmosphere, and a solution of borane-THF complex (1M in THF; 2.2 ml, 2.2 mmol) was added and the resulting solution was stirred at ambient temperature overnight. An additional solution of borane-THF complex (1M in THF; 2.2 ml, 2.2 mmol) was added. The resulting mixture was stirred at ambient for further 6 hrs. The mixture was diluted with NH3 in MeOH (7N, 20 ml) and stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, diluted with EtOAc (75 ml), washed with water (40 ml), and dried (Na2SO4). Evaporation of the volatiles under reduced pressure afforded a concentrate, which was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes) to provide the title compound (280 mg, yield: 48%).

後処理

  1. stirringThe resulting mixture was stirred at ambient for further 6 hrs
  2. stirringstirred at room temperature overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with EtOAc (75 ml)
  5. washwashed with water (40 ml)
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the volatiles under reduced pressure
  8. customafforded a concentrate, which
  9. customwas purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-6319a21e3c5b49afb50b84a31807277f
出典データセット
uspto-grants-2016_02
特許番号
US09248140B2

反応ノート

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