Methanol → 3-((3-((4-(Piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)sulfonyl)benzoic acid

HRID 625270Notes

Reaction equation

HRID 625270 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=3)[CH2:19][S:20][C:21]3[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=3)[C:24]([OH:26])=[O:25])=[O:15])=[C:9]([C:33]3[CH:38]=[C:37]([C:39](=[O:52])[NH:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[C:44]([C:48]([F:51])([F:50])[F:49])[CH:43]=4)[CH:36]=[CH:35][N:34]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1COCC1.[OH2:58].OOS([O-])=O.[K+].C[OH:66]>C(OCC)(=O)C.[Pd]>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=3)[CH2:19][S:20]([C:21]3[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=3)[C:24]([OH:26])=[O:25])(=[O:66])=[O:58])=[O:15])=[C:9]([C:33]3[CH:38]=[C:37]([C:39](=[O:52])[NH:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[C:44]([C:48]([F:51])([F:49])[F:50])[CH:43]=4)[CH:36]=[CH:35][N:34]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 887Methanol3×HCID 962WaterHCID 8028TetrahydrofuranHCID 23707502Potassium hydroxy sulfiteHCID 665867593-(3-(4-(Piperidin-1-yl)-2-(4-(3-(trifluoromethyl)-benzylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)benzylthio)benzoic acid

Product 1

HCID 696315823-((3-((4-(Piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)sulfonyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 25 mg of 3-((3-((4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)thio)benzoic acid 8.25 in 2 mL of a 2:1:1 mixture of THF, methanol, and water was treated with 110 mg of Oxone®. The mixture was stirred for 2 h and then it was diluted with ethyl acetate. The organic phase was washed with water, which caused a precipitate to form. The precipitate was redissolved by adding methanol. The organic phase was separated and filtered. Evaporation of the solvent gave a white solid. This solid was dissolved in methanol and treated with 5 mg of 5% Pd/C. The mixture was stirred under a hydrogen atmosphere for 15 minutes, and then it was filtered. The solvent was evaporated and the residue was purified by reverse phase HPLC, eluting with 0.05% TFA in a water/acetonitrile gradient. The process yielded 8.6 mg of product. MS (ES, m/z) 757 [M+H]+.

Workup

  1. washThe organic phase was washed with water, which
  2. customto form
  3. dissolutionThe precipitate was redissolved
  4. customThe organic phase was separated
  5. filtrationfiltered
  6. customEvaporation of the solvent
  7. customgave a white solid
  8. stirringThe mixture was stirred under a hydrogen atmosphere for 15 minutes
  9. filtrationit was filtered
  10. customThe solvent was evaporated
  11. customthe residue was purified by reverse phase HPLC
  12. washeluting with 0.05% TFA in a water/acetonitrile gradient

Sources & evidence

ORD record
ord-ec236b62f2e04ec5a2377e6eed2bf271
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

Loading…