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

HRID 1408024Notes

Reaction equation

HRID 1408024 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([CH:48]=[CH:49][CH:50]=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]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[CH:32]=[C:33]([CH:45]=[CH:46][CH:47]=2)[CH2:34][S:35][CH2:36][CH2:37][C:38]([O:40]C(C)(C)C)=[O:39])=[O:30])[CH:11]=1)=[O:9].FC(F)(F)C(O)=O>ClCCl>[F:52][C:2]([F:1])([F:51])[C:3]1[CH:4]=[C:5]([CH:48]=[CH:49][CH:50]=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]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[CH:32]=[C:33]([CH:45]=[CH:46][CH:47]=2)[CH2:34][S:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[O:30])[CH:11]=1)=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66586738Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-morpholinophenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 665868403-(3-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-morpholinophenyl)carbamoyl)benzylthio)propanoic acidYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-morpholinophenyl)carbamoyl)benzylthio)propanoate (100 mg, 0.14 mmol, 1.00 equiv) in dichloromethane (5 mL), and trifluoroacetic acid (0.1 mL). The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. 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 14 mg (15%) of a yellow solid. 1H-NMR (300 MHz, CDCl3, ppm): δ 13.55 (s, 1H), 9.09 (s, 1H), 8.96-8.78 (m, 2H), 8.72 (s, 1H), 8.65 (s, 1H), 8.25-8.09 (m, 3H), 8.05-7.90 (m, 8H), 4.73 (d, J=5.4 Hz, 2H), 4.13 (s, 4H), 3.82 (s, 2H), 3.47 (s, 4H), 2.75-2.57 (m, 4H). MS (ES, m/z): 679 [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-69e4823f29a348719ce4a124bea0eccc
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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