Hydrochloric Acid → 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)(ethyl)amino)ethyl dihydrogen phosphate, hydrochloride salt

HRID 1476341Notes

Reaction equation

HRID 1476341 reaction equation
[P:1]([O:13][CH2:14][CH2:15][N:16]([CH2:19][CH2:20][C@@H:21]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([S:37](=[O:69])(=[O:68])[NH:38][C:39](=[O:67])[C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][CH:49]([C@H:52]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=4[C:60]4[CH:65]=[CH:64][C:63]([Cl:66])=[CH:62][CH:61]=4)[OH:53])[CH2:48][CH2:47]3)=[CH:42][CH:41]=2)=[CH:33][C:32]=1[S:70]([C:73]([F:76])([F:75])[F:74])(=[O:72])=[O:71])[CH2:22][S:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:17][CH3:18])([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].Cl>C(Cl)Cl.CO>[ClH:66].[P:1]([OH:8])([OH:3])([O:13][CH2:14][CH2:15][N:16]([CH2:19][CH2:20][C@@H:21]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([S:37](=[O:69])(=[O:68])[NH:38][C:39](=[O:67])[C:40]2[CH:41]=[CH:42][C:43]([N:46]3[CH2:51][CH2:50][CH:49]([C@H:52]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=4[C:60]4[CH:61]=[CH:62][C:63]([Cl:66])=[CH:64][CH:65]=4)[OH:53])[CH2:48][CH2:47]3)=[CH:44][CH:45]=2)=[CH:33][C:32]=1[S:70]([C:73]([F:74])([F:76])[F:75])(=[O:71])=[O:72])[CH2:22][S:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:17][CH3:18])=[O:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 87125282Di-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)(ethyl)amino)ethyl phosphate2×

Product 1

HCID 1317327872-(((R)-3-(4-(N-(4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)(ethyl)amino)ethyl dihydrogen phosphate, hydrochloride saltYield 143.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 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)(ethyl)amino)ethyl phosphate (INTERMEDIATE 55, 147 mg, 0.14 mmol) in DCM (3.17 ml) was treated with a solution of HCl (4M in dioxane, 0.60 ml). When the addition was completed, a white precipitate was observed. The mixture was diluted with MeOH after an hour and the volatiles were evaporated under reduced pressure to give a gummy residue. The material was dissolved in MeOH, and diluted with ˜20 ml DCM, resulting in a white precipitate. The mixture was concentrated under reduced pressure to provide a white solid. The material was triturated in 10-15 ml CH2Cl2, and dried under high vacuum to provide the title compound (108 mg, 95%).

Workup

  1. additionWhen the addition
  2. customthe volatiles were evaporated under reduced pressure
  3. customto give a gummy residue
  4. customresulting in a white precipitate
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customto provide a white solid
  7. customThe material was triturated in 10-15 ml CH2Cl2
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-95970c04f29e4f06b05fb3492447fc17
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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