Trifluoroacetic acid → HCID 87954590, compound

HRID 1814319Notes

Reaction equation

HRID 1814319 reaction equation
C([O:5][C:6](=[O:36])[CH2:7][C@H:8]([NH:11][S:12]([C:15]1[C:16]([O:23][CH2:24][CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=[CH:28][CH:27]=2)=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=1)(=[O:14])=[O:13])[CH:9]=[O:10])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:22][O:21][C:18]1[N:17]=[C:16]([O:23][CH2:24][CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=[CH:28][CH:27]=2)[C:15]([S:12]([NH:11][C@H:8]([CH:9]=[O:10])[CH2:7][C:6]([OH:36])=[O:5])(=[O:14])=[O:13])=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 87969955HCID 87969955, compound

Product 1

HCID 87954590HCID 87954590, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-3-[6-Methoxy-2-(2-quinolin-4-yl-ethoxy)-pyridin-3-sulfonylamino]-4-oxo-butyric acid tert-butyl ester (0.18 g, 0.35 mmol) was stirred in 5 mL of a solution of 25% TFA in CH2Cl2 at room temperature for 2 h. Analytical HPLC indicated the reaction was complete. The reaction mixture was concentrated. Residual TFA was azeotroped with toluene. The crude product was purified by preparative-scale reverse phase HPLC (0 to 30% acetonitrile in H2O with 0.1% TFA over 2.5 hours at 15 mL/min on Vydac 2.5×25 cm C18 column) to give 0.053 g (0.12 mmol, 33%) of (S)-3-[6-methoxy-2-(2-quinolin-4-yl-ethoxy)-pyridin-3-sulfonylamino]-4-oxo-butryric acid as a fluffy white solid. MS (APCI) m/z 460.2 (M+1). 1H NMR (300 MHz) CD3OD 9.03 (m, 1H), 8.63 (d, J=8.4 Hz, 1H), 7.94-8.23 (m, 5H), 6.39 (d, J=8.4 Hz, 1H), 4.97 (m, 2H), 4.43 (dd, 1H), 3.96 (m, 2H), 3.88 (d, 3H), 3.48 (m, 1H), 2.46-2.60 (m, 1H), 2.24-2.38 (m, 1H)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customResidual TFA was azeotroped with toluene
  3. customThe crude product was purified by preparative-scale reverse phase HPLC (0 to 30% acetonitrile in H2O with 0.1% TFA over 2.5 hours at 15 mL/min on Vydac 2.5×25 cm C18 column)
  4. customto give 0.053 g (0.12 mmol, 33%) of (S)-3-[6-methoxy-2-(2-quinolin-4-yl-ethoxy)-pyridin-3-sulfonylamino]-4-oxo-butryric acid as a fluffy white solid

Sources & evidence

ORD record
ord-3b79f4e6b8dd408988abe485c80c099c
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

Loading…