Trifluoroacetic acid → 3-(3-(2-(1-(3,4-dimethylphenyl)-1H-pyrazol-3-ylcarbamoyl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoic acid

HRID 926862Notes

Reaction equation

HRID 926862 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[CH:22]=[C:21]([N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[CH:20]=[CH:19][C:18]=3[NH:29][C:30]([C:32]3[CH:33]=[C:34]([CH:46]=[CH:47][CH:48]=3)[CH2:35][S:36][CH2:37][CH2:38][C:39]([O:41]C(C)(C)C)=[O:40])=[O:31])=[O:16])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].FC(F)(F)C(O)=O>ClCCl>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[CH:22]=[C:21]([N:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)[CH:20]=[CH:19][C:18]=3[NH:29][C:30]([C:32]3[CH:33]=[C:34]([CH:46]=[CH:47][CH:48]=3)[CH2:35][S:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:31])=[O:16])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66587576tert-butyl 3-(3-(2-(1-(3,4-dimethylphenyl)-1H-pyrazol-3-ylcarbamoyl)-4-(piperidin-1-yl)phenylcarbamoyl)benzylthio)propanoate

Product 1

HCID 566437253-(3-(2-(1-(3,4-dimethylphenyl)-1H-pyrazol-3-ylcarbamoyl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoic acidYield 63.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of tert-butyl 3-(3-(2-(1-(3,4-dimethylphenyl)-1H-pyrazol-3-ylcarbamoyl)-4-(piperidin-1-yl)phenylcarbamoyl)benzylthio)propanoate (150 mg, 0.22 mmol, 1.00 equiv) in dichloromethane (4 mL), and trifluoroacetic acid (2 mL). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The crude product (100 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 85.3 mg (62%) of a white solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.70(s, 1H), 11.44(s, 1H), 8.41(m, 2H), 7.91(s, 1H), 7.78(m, 1H), 7.68(m, 1H), 7.62(m, 1H), 7.58(m, 3H), 7.40(m, 1H), 7.23(m, 1H), 6.92(s, 1H), 3.86(s, 2H), 3.36(m, 4H), 2.62(m, 2H), 2.29(m, 6H), 1.60(m, 6H). MS (ES, m/z): 612 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product (100 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-8bcae84407cf4ec7b12a5392d0802658
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Reaction notes

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