Borane;tetrahydrofuran → (R)-4-(4-(4-(2-(tert-Butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1771171Notes

Reaction equation

HRID 1771171 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27](=O)[CH2:28][C@@H:29]([NH:38][C:39]2[CH:44]=[CH:43][C:42]([S:45]([NH2:48])(=[O:47])=[O:46])=[CH:41][C:40]=2[S:49]([C:52]([F:55])([F:54])[F:53])(=[O:51])=[O:50])[CH2:30][S:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:23][CH2:22]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]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][C@@H:29]([NH:38][C:39]2[CH:44]=[CH:43][C:42]([S:45]([NH2:48])(=[O:46])=[O:47])=[CH:41][C:40]=2[S:49]([C:52]([F:54])([F:53])[F:55])(=[O:50])=[O:51])[CH2:30][S:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:23][CH2:22]1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 66723668(R)-4-(4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Product 1

HCID 66723648(R)-4-(4-(4-(2-(tert-Butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideYield 25.5%

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-4-(4-(4-(2-(tert-Butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 21, 0.98 g, 1.15 mmol) was dissolved in THF (4.6 ml), under a nitrogen atmosphere, and a solution of borane-THF complex (1M in THF; 6.93 ml, 6.93 mmol) was added. 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 (245 mg, yield: 25%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with EtOAc (75 ml)
  3. washwashed with water (40 ml)
  4. dry with materialdried (Na2SO4)
  5. customEvaporation of the volatiles under reduced pressure
  6. customafforded a concentrate, which
  7. customwas purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5193fbf485ed45938f3734f0e4c92300
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

Loading…