Diisopropylethylamine → (R)-4-(4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1476270Notes

Reaction equation

HRID 1476270 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:34]1([S:40][CH2:41][C@H:42]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([S:54](=[O:57])(=[O:56])[NH2:55])=[CH:50][C:49]=2[S:58]([C:61]([F:64])([F:63])[F:62])(=[O:60])=[O:59])[CH2:43][C:44](O)=[O:45])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[Si:65]([O:82][CH2:83][CH2:84][N:85]1[CH2:90][CH2:89][NH:88][CH2:87][CH2:86]1)([C:78]([CH3:81])([CH3:80])[CH3:79])([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1>CC(N(C)C)=O.CCOC(C)=O>[Si:65]([O:82][CH2:83][CH2:84][N:85]1[CH2:90][CH2:89][N:88]([C:44](=[O:45])[CH2:43][C@@H:42]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([S:54]([NH2:55])(=[O:56])=[O:57])=[CH:50][C:49]=2[S:58]([C:61]([F:64])([F:62])[F:63])(=[O:60])=[O:59])[CH2:41][S:40][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:87][CH2:86]1)([C:78]([CH3:79])([CH3:80])[CH3:81])([C:72]1[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=1)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 453571091-(2-(tert-Butyldiphenylsilyloxy)ethyl)piperazine2×HCID 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2×

Product 1

HCID 66723668(R)-4-(4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideYield 117.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Procedure

HATU (0.915 g, 2.41 mmol) and DIPEA (0.701 ml, 4.01 mmol) were added sequentially to a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino) butanoic acid (INTERMEDIATE 8, 1.0 g, 2.01 mmol) and 1-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazine (INTERMEDIATE 20, 0.894 g, 2.21 mmol) in DMA (2.0 ml). Additional DMA (1.7 ml) was added and the resulting mixture was stirred at room temperature for 2 hrs. The mixture was diluted with EtOAc and the organic layer was washed with H2O (2×), 1N NaHSO4 (aq.) and saturated aq. NaHCO3. The organic layer was dried (Na2SO4), and concentrated under reduced pressure to provide the title product (2.0 g, yield: quantitative), which was used in the preparation of INTERMEDIATE 22 without further purification.

Workup

  1. washthe organic layer was washed with H2O (2×), 1N NaHSO4 (aq.) and saturated aq. NaHCO3
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3a7cfaa420f742eb9c4db0e91c1ae089
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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