Trifluoroacetic acid → 3-(3-(2-(4-(4-Morpholinobenzylcarbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)-phenylcarbamoyl)benzylthio) propanoic acid

HRID 1408158Notes

Reaction equation

HRID 1408158 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:54]=[CH:53][C:10]([CH2:11][NH:12][C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([C:21]4[CH:26]=[C:25]([N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)[CH:24]=[CH:23][C:22]=4[NH:33][C:34]([C:36]4[CH:37]=[C:38]([CH:50]=[CH:51][CH:52]=4)[CH2:39][S:40][CH2:41][CH2:42][C:43]([O:45]C(C)(C)C)=[O:44])=[O:35])[CH:16]=3)=[O:14])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>ClCCl>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:54]=[CH:53][C:10]([CH2:11][NH:12][C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([C:21]4[CH:26]=[C:25]([N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)[CH:24]=[CH:23][C:22]=4[NH:33][C:34]([C:36]4[CH:37]=[C:38]([CH:50]=[CH:51][CH:52]=4)[CH2:39][S:40][CH2:41][CH2:42][C:43]([OH:45])=[O:44])=[O:35])[CH:16]=3)=[O:14])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 66586822Tert-butyl 3-(3-(2-(4-(4-morpholinobenzylcarbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoate

Product 1

HCID 665881463-(3-(2-(4-(4-Morpholinobenzylcarbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)-phenylcarbamoyl)benzylthio) propanoic acidYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 3-(3-(2-(4-(4-morpholinobenzylcarbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoate (170 mg, 0.20 mmol, 1.00 equiv, 86%) in dichloromethane (20 mL), and trifluoroacetic acid (2 mL). The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. The solution was adjusted to pH 7-8 with NaHCO3 (aq). The resulting solution was extracted with 3×30 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×30 mL of brine, dried over NaSO4 and concentrated under vacuum. The crude product (120 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 17 mg (13%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 8.96 (s, 1H), 8.49 (m, 1H), 8.34 (s, 1H), 7.79 (m, 4H), 7.54 (m, 3H), 7.16 (m, 2H), 6.89 (m, 2H), 4.42 (s, 2H), 3.86 (s, 2H), 3.70 (m, 5H), 3.49 (s, 4H), 3.04 (m, 4H), 2.60 (m, 2H), 1.78 (m, 6H). MS (ES, m/z): 694 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. extractionThe resulting solution was extracted with 3×30 mL of dichloromethane
  4. washThe resulting mixture was washed with 1×30 mL of brine
  5. dry with materialdried over NaSO4
  6. concentrationconcentrated under vacuum
  7. customThe crude product (120 mg) was purified by reverse phase HPLC
  8. washeluting with a water/CH3CN gradient
  9. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-fad4037687fa4a8ba66956efb6ecd082
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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