Diisopropylethylamine → (R)-N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluorom ethylsulfonyl)phenylamino)butanamide

HRID 1476273노트

반응식

HRID 1476273 반응식
[Si:1]([O:18][CH2:19][CH2:20][NH:21][CH2:22][CH3:23])([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.P(ON1C(=O)C2C=CC=CC=2N=N1)(OCC)(OCC)=O.CCN(C(C)C)C(C)C.[C:53]1([S:59][CH2:60][C@H:61]([NH:66][C:67]2[CH:72]=[CH:71][C:70]([S:73](=[O:76])(=[O:75])[NH2:74])=[CH:69][C:68]=2[S:77]([C:80]([F:83])([F:82])[F:81])(=[O:79])=[O:78])[CH2:62][C:63]([OH:65])=O)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C1COCC1>[Si:1]([O:18][CH2:19][CH2:20][N:21]([CH2:22][CH3:23])[C:63](=[O:65])[CH2:62][C@@H:61]([NH:66][C:67]1[CH:72]=[CH:71][C:70]([S:73](=[O:75])(=[O:76])[NH2:74])=[CH:69][C:68]=1[S:77]([C:80]([F:81])([F:82])[F:83])(=[O:79])=[O:78])[CH2:60][S:59][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 580801592-(tert-butyldiphenylsilyloxy)-N-ethylethanamine2회HCID 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2회

생성물 1

HCID 66723918(R)-N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluorom ethylsulfonyl)phenylamino)butanamide수율 91.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

2-(tert-Butyldiphenylsilyloxy)-N-ethylethanamine (INTERMEDIATE 23, 0.263 g, 0.80 mmol) in THF (2.5 ml), diethyl 4-oxobenzo[d][1,2,3]triazin-3(4H)-yl phosphate (0.480 g, 1.60 mmol) and DIPEA (0.280 ml, 1.60 mmol) were added sequentially to a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid (INTERMEDIATE 8, 0.4 g, 0.80 mmol) in THF (5.0 ml) and the mixture was stirred at room temperature for 3 hrs. The reaction mixture was then concentrated under reduced pressure, diluted with EtOAc and the organic layer was washed with 1N aq. NaHSO4 and saturated aq. NaHCO3. The organic layer was dried (Na2SO4), concentrated under reduced pressure to give a residue, which was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes) to provide the title product (590 mg, yield: 91%).

후처리

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. additiondiluted with EtOAc
  3. washthe organic layer was washed with 1N aq. NaHSO4 and saturated aq. NaHCO3
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue, which
  7. customwas purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-6d7495a6aa0549a3a36e59acd908b269
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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