Trifluoroacetic acid → CP-533,536 metabolite M4

HRID 23798Notes

Reaction equation

HRID 23798 reaction equation
C([O:5][C:6](=[O:38])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([CH3:37])([CH3:36])[CH2:34][OH:35])=[CH:29][CH:28]=2)[S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH:10]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[OH:35][CH2:34][C:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][N:16]([CH2:15][C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=2)[O:8][CH2:7][C:6]([OH:38])=[O:5])[S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])=[CH:28][CH:29]=1)([CH3:37])[CH3:36]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69731661(3-{[[4-(2-Hydroxy-1,1-dimethyl-ethyl)-benzyl]-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester

Product 1

HCID 9956982CP-533,536 metabolite M4Yield 35.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (3-{[[4-(2-hydroxy-1,1-dimethyl-ethyl)-benzyl]-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester (108 mg, 0.199 mmol) in CH2Cl2 (2 mL) was cooled to 0° C. and trifluoroacetic acid (1 mL) was added. The reaction was stirred at room temperature for 1 h. The solution was concentrated in vacuo, by azeotroping with CH2Cl2 (3×). The residue was dissolved in THF and 1N HCl (0.4 mL) was added. The solution was concentrated in vacuo, azeotroping with CH2Cl2 (3×). Purification by radial chromatography using a solvent gradient (CH2Cl2 to 20% MeOH in CH2Cl2) provided the title compound (34 mg). 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 1H), 8.69 (s, 1H), 8.11 (d, 1H), 7.52 (m, 1H), 7.21 (d, 2H), 7.09 (m, 1H), 7.02 (d, 2H), 6.76 (d, 1H), 6.70 (m, 2H), 4.86 (s, 2H), 4.32 (m, 4H), 3.48 (s, 2H), 1.22 (s, 6H); MS 485.2 (M+1), 483.4 (M−1).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customby azeotroping with CH2Cl2 (3×)
  3. dissolutionThe residue was dissolved in THF
  4. addition1N HCl (0.4 mL) was added
  5. concentrationThe solution was concentrated in vacuo
  6. customazeotroping with CH2Cl2 (3×)
  7. customPurification by radial chromatography

Sources & evidence

ORD record
ord-241efd5aa9ae47029a6b2b2693b89392
Source dataset
uspto-grants-2005_02
Patent number
US06852863B2

Reaction notes

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