Trifluoroacetic acid → 3-(3-((4-(Piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoic acid

HRID 2406100Notes

Reaction equation

HRID 2406100 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([O:25]C(C)(C)C)=[O:24])=[O:15])=[C:9]([C:33](=[O:51])[NH:34][C:35]3[CH:40]=[N:39][C:38]([C:41]4[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:50])([F:49])[F:48])[CH:42]=4)=[CH:37][N:36]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:15])=[C:9]([C:33](=[O:51])[NH:34][C:35]3[CH:40]=[N:39][C:38]([C:41]4[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:50])([F:48])[F:49])[CH:42]=4)=[CH:37][N:36]=3)[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66586944Tert-butyl 3-(3-((4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 566023953-(3-((4-(Piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoic acidYield 9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of tert-butyl 3-(3-((4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoate (140 mg, 0.19 mmol, 1.00 equiv) in dichloromethane (2 mL). This was followed by dropwise addition of 2,2,2-trifluoroacetic acid (1 mL) with stirring. The resulting solution was stirred for 2 h at 25° C. in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 11 mg (9%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.47 (s, 1H), 11.01 (s, 1H), 9.47 (s, 1H), 9.23 (s, 1H), 8.44 (d, J=4.5 Hz, 2H), 8.10 (d, J=9 Hz, 1H), 7.80 (m, 4H), 7.51 (m, 3H), 7.36 (m, 1H), 3.83 (s, 2H), 3.41 (s, 4H), 2.60 (d, 2H), 1.60 (m, 6H). MS (ES, m/z): 644 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. stirringThe resulting solution was stirred for 2 h at 25° C. in an oil bath
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. customThe crude product was purified by reverse phase HPLC
  5. washeluting with a water/CH3CN gradient
  6. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-9879dab2d75f4d18a8ac00b5b342fddb
Source dataset
uspto-grants-2014_08
Patent number
US08809339B2

Reaction notes

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