1,2-Dichloroethane → Di-tert-butyl 2-(4-((R)-3-(4-(N-(4-(4-((R)-(tert-butyl dimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperazin-1-yl)ethyl phosphate

HRID 1476297Notes

Reaction equation

HRID 1476297 reaction equation
[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[P:38]([O:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][N:56]([CH2:59][CH2:60][C@@H:61]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([S:77](=[O:80])(=[O:79])[NH2:78])=[CH:73][C:72]=2[S:81]([C:84]([F:87])([F:86])[F:85])(=[O:83])=[O:82])[CH2:62][S:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[CH2:55][CH2:54]1)([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[P:38]([O:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][N:56]([CH2:59][CH2:60][C@@H:61]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([S:77](=[O:79])(=[O:80])[NH:78][C:20](=[O:21])[C:19]3[CH:18]=[CH:17][C:16]([N:13]4[CH2:12][CH2:11][CH:10]([C@@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3])[C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[C:31]5[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=5)[CH2:15][CH2:14]4)=[CH:24][CH:23]=3)=[CH:73][C:72]=2[S:81]([C:84]([F:87])([F:86])[F:85])(=[O:83])=[O:82])[CH2:62][S:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[CH2:55][CH2:54]1)([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 58080201(R)-4-(4-((tert-Butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid2×HCID 66723554(R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate2×

Product 1

HCID 58080246Di-tert-butyl 2-(4-((R)-3-(4-(N-(4-(4-((R)-(tert-butyl dimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperazin-1-yl)ethyl phosphate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(R)-4-(4-((tert-butyldimethylsilyloxy)(4 ′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 13, 170 mg, 0.32 mmol), (R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate (INTERMEDIATE 61, 275 mg, 0.35 mmol), DMAP (116 mg, 0.95 mmol) and EDC (122 mg, 0.63 mmol) were dissolved in DCM (3.2 ml). The reaction mixture was stirred at r.t. for 72 hours. The mixture was diluted with DCM (10 ml) and washed with NaHCO3 solution (saturated, aq., 5 ml) and brine (5 ml). The collected organic layer was dried over Na2SO4 and concentrated to give the title compound (446 mg, yield: almost quantitative). The title compound was used in the preparation of EXAMPLE 10 without further purification.

Workup

  1. washwashed with NaHCO3 solution (saturated, aq., 5 ml) and brine (5 ml)
  2. dry with materialThe collected organic layer was dried over Na2SO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-3d3f8fb27af647408e59a3d41738f3b3
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

Loading…