Hydrochloric Acid → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1771231Notes

Reaction equation

HRID 1771231 reaction equation
Cl.O1CCOCC1.[Si]([O:15][CH2:16][CH2:17][N:18]([CH2:77][CH3:78])[CH2:19][CH2:20][C@@H:21]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH:40][C:41](=[O:69])[C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][CH:51]([C@H:54]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=4[C:62]4[CH:67]=[CH:66][C:65]([Cl:68])=[CH:64][CH:63]=4)[OH:55])[CH2:50][CH2:49]3)=[CH:44][CH:43]=2)(=[O:39])=[O:38])=[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)(C(C)(C)C)(C)C>C(Cl)Cl>[Cl:68][C:65]1[CH:66]=[CH:67][C:62]([C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=2[C@H:54]([OH:55])[CH:51]2[CH2:50][CH2:49][N:48]([C:45]3[CH:46]=[CH:47][C:42]([C:41]([NH:40][S:37]([C:34]4[CH:35]=[CH:36][C:31]([NH:30][C@H:21]([CH2:20][CH2:19][N:18]([CH2:77][CH3:78])[CH2:17][CH2:16][OH:15])[CH2:22][S:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)=[C:32]([S:70]([C:73]([F:74])([F:75])[F:76])(=[O:71])=[O:72])[CH:33]=4)(=[O:38])=[O:39])=[O:69])=[CH:43][CH:44]=3)[CH2:53][CH2:52]2)=[CH:63][CH:64]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 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)benzamide2×

Product 1

HCID 566506704-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of HCl in dioxane (4M, 11.18 ml, 44.70 mmol) was added slowly to a light yellow solution of 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 (INTERMEDIATE 66, 2.4 g, 2.24 mmol) in DCM (11.2 ml) at 0° C. Once the addition was complete, the ice bath was removed. The resulting solution was allowed to warm to r.t. and stirred for 1 hour before being concentrated under reduced pressure to half volume and diluted with ethyl acetate. The resulting mixture was washed with sodium bicarbonate (saturated, aqueous) and sodium chloride (saturated, aqueous) before being dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, silica gel, 0→20% methanol in ethyl acetate for 30 min) to provide the title compound (1.64 g, yield: 76%).

Workup

  1. additionOnce the addition
  2. customthe ice bath was removed
  3. concentrationbefore being concentrated under reduced pressure to half volume
  4. additiondiluted with ethyl acetate
  5. washThe resulting mixture was washed with sodium bicarbonate (saturated, aqueous) and sodium chloride (saturated, aqueous)
  6. dry with materialbefore being dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate was purified by column chromatography (ISCO, silica gel, 0→20% methanol in ethyl acetate for 30 min)

Sources & evidence

ORD record
ord-bd74a57d073b4159b9f169790061fe27
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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