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)(methyl)amino)ethyl dihydrogen phosphate, hydrochloride salt

HRID 1476342Notes

Reaction equation

HRID 1476342 reaction equation
[P:1]([O:13][CH2:14][CH2:15][N:16]([CH2:18][CH2:19][C@@H:20]([NH:29][C:30]1[CH:35]=[CH:34][C:33]([S:36](=[O:68])(=[O:67])[NH:37][C:38](=[O:66])[C:39]2[CH:44]=[CH:43][C:42]([N:45]3[CH2:50][CH2:49][CH:48]([C@H:51]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=4[C:59]4[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][CH:60]=4)[OH:52])[CH2:47][CH2:46]3)=[CH:41][CH:40]=2)=[CH:32][C:31]=1[S:69]([C:72]([F:75])([F:74])[F:73])(=[O:71])=[O:70])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:17])([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].Cl>C(Cl)Cl.CO>[ClH:65].[P:1]([OH:8])([OH:3])([O:13][CH2:14][CH2:15][N:16]([CH2:18][CH2:19][C@@H:20]([NH:29][C:30]1[CH:35]=[CH:34][C:33]([S:36](=[O:68])(=[O:67])[NH:37][C:38](=[O:66])[C:39]2[CH:40]=[CH:41][C:42]([N:45]3[CH2:50][CH2:49][CH:48]([C@H:51]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=4[C:59]4[CH:60]=[CH:61][C:62]([Cl:65])=[CH:63][CH:64]=4)[OH:52])[CH2:47][CH2:46]3)=[CH:43][CH:44]=2)=[CH:32][C:31]=1[S:69]([C:72]([F:73])([F:75])[F:74])(=[O:70])=[O:71])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:17])=[O:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 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 phosphate2×

Product 1

HCID 1317327882-(((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 dihydrogen phosphate, hydrochloride saltYield 173.8%

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)(methyl)amino)ethyl phosphate (INTERMEDIATE 56, 140 mg, 0.13 mmol) in DCM (3 ml) was treated with a solution of HCl (4M in dioxane, 0.6 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 (120 mg, yield: 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-aca8db24309f4e2f8d0802fd6ba1171e
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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