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

HRID 1771173Notes

Reaction equation

HRID 1771173 reaction equation
[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

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 580801592-(tert-butyldiphenylsilyloxy)-N-ethylethanamine2×HCID 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2×

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-9078a8eba4b84137b03c1676629c3136
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

Loading…