Trifluoroacetic acid → 3-(3-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(bis(2-methoxyethyl)amino)phenyl)carbamoyl)benzylthio)propanoic acid

HRID 625293Notes

Reaction equation

HRID 625293 reaction equation
[F:1][C:2]([F:55])([F:54])[C:3]1[CH:4]=[C:5]([CH:51]=[CH:52][CH:53]=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]([CH2:27][CH2:28][O:29][CH3:30])[CH2:23][CH2:24][O:25][CH3:26])[CH:19]=[CH:18][C:17]=2[NH:31][C:32]([C:34]2[CH:35]=[C:36]([CH:48]=[CH:49][CH:50]=2)[CH2:37][S:38][CH2:39][CH2:40][C:41]([O:43]C(C)(C)C)=[O:42])=[O:33])[CH:11]=1)=[O:9].FC(F)(F)C(O)=O>ClCCl>[F:55][C:2]([F:1])([F:54])[C:3]1[CH:4]=[C:5]([CH:51]=[CH:52][CH:53]=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]([CH2:27][CH2:28][O:29][CH3:30])[CH2:23][CH2:24][O:25][CH3:26])[CH:19]=[CH:18][C:17]=2[NH:31][C:32]([C:34]2[CH:35]=[C:36]([CH:48]=[CH:49][CH:50]=2)[CH2:37][S:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[O:33])[CH:11]=1)=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66586851Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(bis(2-methoxyethyl)amino)phenyl)-carbamoyl)benzylthio)propanoate

Product 1

HCID 665879453-(3-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(bis(2-methoxyethyl)amino)phenyl)carbamoyl)benzylthio)propanoic acid

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-(bis(2-methoxyethyl)amino)phenyl)-carbamoyl)benzylthio)propanoate (160 mg, 0.21 mmol, 1.00 equiv) in dichloromethane (8 mL), and trifluoroacetic acid (2 mL). The resulting solution was stirred for 4 h at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The crude product (125 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 81.1 mg (41%) of as a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.86 (s, 1H), 9.49 (t, J=5.7 Hz, 1H), 8.94 (d, J=5.1 Hz, 1H), 8.25 (s, 1H), 8.12 (d, J=6.5 Hz, 1H), 7.82 (s, 2H), 7.71 (m, 2H), 7.62 (m, 5H), 7.15 (d, J=2.4 Hz, 1H), 6.90 (m, 1H), 4.61 (d, J=6.0 Hz, 2H), 3.87 (s, 2H), 3.56 (m, 8H), 3.27 (s, 6H), 2.63 (m, 2H), 2.51 (m, 2H). MS (ES, m/z): 725 [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 (125 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA
  6. customThe product was obtained as 81.1 mg (41%) of as a yellow solid

Sources & evidence

ORD record
ord-404625a56856472a89b2e48d717cbba1
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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