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

HRID 1771174노트

반응식

HRID 1771174 반응식
[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

참가 물질

6

반응물 2

HCID 2723981Borane;tetrahydrofuran2회HCID 66723918(R)-N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluorom ethylsulfonyl)phenylamino)butanamide2회

생성물 1

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

시약·촉매·용매 3

HCID 222Ammonia용매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

(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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-6319a21e3c5b49afb50b84a31807277f
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09248140B2

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