Trifluoroacetic acid → 3-((3-((4-(Dipropylamino)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)thio)propanoic acid

HRID 1408043Notes

Reaction equation

HRID 1408043 reaction equation
[F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([CH:49]=[CH:50][CH:51]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])[CH:19]=[CH:18][C:17]=2[NH:29][C:30]([C:32]2[CH:33]=[C:34]([CH:46]=[CH:47][CH:48]=2)[CH2:35][S:36][CH2:37][CH2:38][C:39]([O:41]C(C)(C)C)=[O:40])=[O:31])[CH:11]=1)=[O:9].FC(F)(F)C(O)=O>ClCCl>[CH2:26]([N:22]([CH2:23][CH2:24][CH3:25])[C:20]1[CH:19]=[CH:18][C:17]([NH:29][C:30]([C:32]2[CH:33]=[C:34]([CH:46]=[CH:47][CH:48]=2)[CH2:35][S:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:31])=[C:16]([C:12]2[CH:11]=[C:10]([C:8](=[O:9])[NH:7][CH2:6][C:5]3[CH:49]=[CH:50][CH:51]=[C:3]([C:2]([F:53])([F:1])[F:52])[CH:4]=3)[CH:15]=[CH:14][N:13]=2)[CH:21]=1)[CH2:27][CH3:28]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66587920Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(dipropylamino)phenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 665868383-((3-((4-(Dipropylamino)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)thio)propanoic acidYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)-benzyl)carbamoyl)pyridin-2-yl)-4-(dipropylamino)phenyl)carbamoyl)benzylthio)-propanoate (320 mg, 0.43 mmol, 1.00 equiv) in dichloromethane (10 mL), and trifluoroacetic acid (1 mL). The resulting solution was stirred overnight at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 108 mg (30%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 9.52 (t, J=6 Hz, 1H), 8.96 (d, J=5.1 Hz, 1H), 8.27 (s, 2H), 7.85 (s, 2H), 7.74 (m, 2H), 7.53 (m, 5H), 7.02 (s, 2H), 4.61 (d, J=5.7 Hz, 2H), 3.87 (s, 2H), 3.39 (s, 4H), 2.61 (m, 2H), 2.50 (m, 2H), 1.53 (t, J=9.3 Hz, 4H), 0.89 (t, J=7.2 Hz, 6H). MS (ES, m/z): 693 [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 (200 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-1b8b5b220a1046f39cd7886d96bcdf19
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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