1,2-Dichloroethane → N-(4-((R)-4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamide

HRID 1771197Notes

Reaction equation

HRID 1771197 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([OH:30])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:71][CH3:72])[CH2:42][CH2:43][C@@H:44]([NH:53][C:54]1[CH:59]=[CH:58][C:57]([S:60]([NH2:63])(=[O:62])=[O:61])=[CH:56][C:55]=1[S:64]([C:67]([F:70])([F:69])[F:68])(=[O:66])=[O:65])[CH2:45][S:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:71][CH3:72])[CH2:42][CH2:43][C@@H:44]([NH:53][C:54]1[CH:59]=[CH:58][C:57]([S:60]([NH:63][C:25](=[O:26])[C:24]2[CH:28]=[CH:29][C:21]([N:18]3[CH2:19][CH2:20][CH:15]([C@H:14]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[OH:30])[CH2:16][CH2:17]3)=[CH:22][CH:23]=2)(=[O:61])=[O:62])=[CH:56][C:55]=1[S:64]([C:67]([F:68])([F:69])[F:70])(=[O:66])=[O:65])[CH2:45][S:46][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)([C:34]([CH3:37])([CH3:35])[CH3:36])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 58080224(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid2×HCID 66723826(R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Product 1

HCID 86661874N-(4-((R)-4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamideYield 62.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(R)-4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 40, 2.15 g, 5.10 mmol), (R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 65, 3.41 g, 5.10 mmol), DMAP (1.87 g, 15.29 mmol) and EDC (1.954 g, 10.19 mmol) were dissolved in DCM (17 ml). The reaction mixture was stirred at r.t. overnight, diluted with DCM (50 ml) and washed with NH4Cl solution (saturated, aq., 20 ml), saturated aq. NaHCO3 (20 ml) and brine (20 ml). The collected organic layer was dried over Na2SO4 and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, 12 g silica gel, eluted with 0→20% MeOH in EtOAc) to provide the title compound (3.41 g, yield: 62%).

Workup

  1. washwashed with NH4Cl solution (saturated, aq., 20 ml), saturated aq. NaHCO3 (20 ml) and brine (20 ml)
  2. dry with materialThe collected organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe concentrate was purified by column chromatography (ISCO, 12 g silica gel, eluted with 0→20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-902246e4a728408a8bcba15c42436a82
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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