(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid → Di-tert-butyl 2-(((R)-3-(4-(N-(4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)(methyl)amino)ethyl phosphate

HRID 1476293Notes

Reaction equation

HRID 1476293 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.[P:31]([O:43][CH2:44][CH2:45][N:46]([CH3:76])[CH2:47][CH2:48][C@@H:49]([NH:58][C:59]1[CH:64]=[CH:63][C:62]([S:65](=[O:68])(=[O:67])[NH2:66])=[CH:61][C:60]=1[S:69]([C:72]([F:75])([F:74])[F:73])(=[O:71])=[O:70])[CH2:50][S:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]>>[P:31]([O:43][CH2:44][CH2:45][N:46]([CH2:47][CH2:48][C@@H:49]([NH:58][C:59]1[CH:64]=[CH:63][C:62]([S:65](=[O:68])(=[O:67])[NH:66][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)=[CH:61][C:60]=1[S:69]([C:72]([F:74])([F:75])[F:73])(=[O:71])=[O:70])[CH2:50][S:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH3:76])([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:32]

Participants

3

Reactant 2

HCID 58080224(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid2×HCID 66723794(R)-di-tert-butyl 2-(methyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate2×

Product 1

HCID 87125252Di-tert-butyl 2-(((R)-3-(4-(N-(4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)(methyl)amino)ethyl phosphateYield 61.5%

Procedure

A similar procedure to that described for INTERMEDIATE 55 utilizing (R)-4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 40, 63 mg, 0.14 mmol) and (R)-di-tert-butyl 2-(methyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate (INTERMEDIATE 54, 105 mg, 0.14 mmol) as starting materials was followed, with subsequent purification by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc) to give the title product (98 mg, yield: 60%).

Workup

  1. customwas followed, with subsequent purification by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-2327073dc905458bab2839e74d45e222
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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