Trifluoroacetic acid → 3-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)-1-(2-(piperidin-4-yl)ethyl)urea HCl salt

HRID 2190336Notes

Reaction equation

HRID 2190336 reaction equation
[Cl:1][C:2]1[S:6][C:5]([NH:7][C:8](=[O:40])[N:9]([CH2:25][CH2:26][CH:27]2[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]2)[CH2:10][CH2:11][CH:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:4][C:3]=1[C:41]1[CH:46]=[CH:45][C:44]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])=[CH:43][CH:42]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[S:6][C:5]([NH:7][C:8](=[O:40])[N:9]([CH2:10][CH2:11][CH:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH2:26][CH:27]2[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]2)=[N:4][C:3]=1[C:41]1[CH:42]=[CH:43][C:44]([NH:47][S:48]([CH3:51])(=[O:49])=[O:50])=[CH:45][CH:46]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57586321Tert-butyl 4-(2-(3-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)ureido)ethyl)piperidine-1-carboxylate

Product 1

HCID 866281263-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)-1-(2-(piperidin-4-yl)ethyl)urea HCl salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To tert-butyl 4-(2-(3-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)ureido)ethyl)piperidine-1-carboxylate (0.29 g, 0.4 mmol) dissolved in DCM (2 ml) was added TFA (0.5 ml, 7 mmol). The resulting mixture was stirred at room temperature for 2 hours. After this time the mixture was concentrated under reduced pressure and the residue triturated with diethyl ether. The pale yellow solid was filtered, washed with ether and dried under vacuum. This solid TFA salt was partitioned between DCM and saturated aqueous NaHCO3. The aqueous was re-extracted with DCM (×2). The combined organic extracts were dried over MgSO4 and concentrated up. The residue was taken up in dry DCM and HCl (2M in diethyl ether) was added. The cloudy solution was conc under reduced pressure and dried under high vac to give 3-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)-1-(2-(piperidin-4-yl)ethyl)urea HCl salt 51 as a pale yellow solid.

Workup

  1. concentrationAfter this time the mixture was concentrated under reduced pressure
  2. customthe residue triturated with diethyl ether
  3. filtrationThe pale yellow solid was filtered
  4. washwashed with ether
  5. customdried under vacuum
  6. customThis solid TFA salt was partitioned between DCM and saturated aqueous NaHCO3
  7. extractionThe aqueous was re-extracted with DCM (×2)
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. concentrationconcentrated up
  10. additionHCl (2M in diethyl ether) was added
  11. customdried under high vac

Sources & evidence

ORD record
ord-d49a17d5b3e14c51b6c1f846696089d7
Source dataset
uspto-grants-2012_12
Patent number
US08324396B2

Reaction notes

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