Trifluoroacetic acid → 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(tetrahydro-2H-pyran-4-yloxy)phenyl)carbamoyl)benzylthio)propanoic acid

HRID 1408032Notes

Reaction equation

HRID 1408032 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]([O:22][CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[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>[F:52][C:2]([F:1])([F:53])[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]([O:22][CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[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]([OH:41])=[O:40])=[O:31])[CH:11]=1)=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66586781tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(tetrahydro-2H-pyran-4-yloxy)phenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 665880403-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(tetrahydro-2H-pyran-4-yloxy)phenyl)carbamoyl)benzylthio)propanoic acid

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-(tetrahydro-2H-pyran-4-yloxy)phenyl)-carbamoyl)benzylthio)propanoate (190 mg, 0.20 mmol, 1.00 equiv, 80%) in dichloromethane (5 mL), and trifluoroacetic acid (1 mL). The resulting solution was stirred for 3 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 82.4 mg (57%) of as a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.94 (d, J=3 Hz, 1H), 8.30 (s, 1H), 8.22 (d, J=9 Hz, 1H), 7.89-7.85 (m, 2H), 7.77 (d, J=9 Hz, 1H), 7.70 (s, 1H), 7.66-7.52 (m, 4H), 7.48-7.43 (m, 2H), 7.19-7.15 (q, J=9 Hz, 1H), 4.69 (s, 3H), 4.01-3.95 (m, 2H), 3.86 (s, 2H), 3.66-3.58 (m, 2H), 2.73-2.68 (m, 2H), 2.59-2.54 (m, 2H), 2.06 (m, 2H), 1.80-1.76 (m, 2H). MS (ES, m/z): 694 [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
  6. customThe product was obtained as 82.4 mg (57%) of as a yellow solid

Sources & evidence

ORD record
ord-7e03a83076b24b77947c860d223040bb
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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