Trifluoroacetic acid → 3-(3-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-chlorophenyl)carbamoyl)benzylthio)propanoic acid

HRID 625307Notes

Reaction equation

HRID 625307 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:43]=[CH:44][CH:45]=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]([Cl:22])[CH:19]=[CH:18][C:17]=2[NH:23][C:24]([C:26]2[CH:27]=[C:28]([CH:40]=[CH:41][CH:42]=2)[CH2:29][S:30][CH2:31][CH2:32][C:33]([O:35]C(C)(C)C)=[O:34])=[O:25])[CH:11]=1)=[O:9].FC(F)(F)C(O)=O>ClCCl>[F:46][C:2]([F:1])([F:47])[C:3]1[CH:4]=[C:5]([CH:43]=[CH:44][CH:45]=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]([Cl:22])[CH:19]=[CH:18][C:17]=2[NH:23][C:24]([C:26]2[CH:27]=[C:28]([CH:40]=[CH:41][CH:42]=2)[CH2:29][S:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:25])[CH:11]=1)=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66587946Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-chlorophenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 665879473-(3-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-chlorophenyl)carbamoyl)benzylthio)propanoic acidYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
15 °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-chlorophenyl)carbamoyl)benzylthio)propanoate (350 mg, 0.51 mmol, 1.00 equiv) in dichloromethane (5.0 mL), and trifluoroacetic acid (581.4 mg, 5.10 mmol, 10.00 equiv). The resulting solution was stirred overnight at 15° C. The resulting mixture was concentrated under vacuum. The crude product (340 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained 250 mg (78%) of a white solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.988 (s, 1H), 12.228 (s, 1H), 9.595-9.560 (m, 1H), 9.020-9.003 (d, J=5.1 Hz, 1H), 8.631-8.601 (d, J=9.0 Hz, 1H), 8.448 (s, 1H), 8.118-8.126 (d, J=2.4 Hz, 1H), 7.917-7.899 (d, J=5.4 Hz, 2H), 7.837-7.812 (d, J=7.5 Hz, 1H), 7.727-7.510 (m, 6H), 4.662-4.643 (d, J=5.7 Hz, 2H), 3.904 (s, 2H), 2.637-2.594 (m, 2H), 2.538 (m, 2H). MS (ES, m/z): 628 [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 (340 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-b8b06981fe2c453c9038415737e88334
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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