3-Pyridinemethanol → 5-[(2,5-Difluorophenyl) [(4-fluorophenyl)sulfonyl]methyl]-4-methyl-N-[(pyridin-3-ylmethoxy)methyl]pyridine-2-carboxamide

HRID 1641751Notes

Reaction equation

HRID 1641751 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:10]1[C:11]([CH3:21])=[CH:12][C:13]([C:16]([NH:18][CH2:19][OH:20])=[O:17])=[N:14][CH:15]=1.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]O)[CH:33]=1.O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:22]([C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)(=[O:24])=[O:23])[C:10]1[C:11]([CH3:21])=[CH:12][C:13]([C:16]([NH:18][CH2:19][O:20][CH2:38][C:34]2[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=2)=[O:17])=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 75103-PyridinemethanolHCID 119996905-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamideHCID 86626551p-Toluenesulfonic acid dihydrate

Product 1

HCID 577365355-[(2,5-Difluorophenyl) [(4-fluorophenyl)sulfonyl]methyl]-4-methyl-N-[(pyridin-3-ylmethoxy)methyl]pyridine-2-carboxamideYield 25%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A benzene solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamide (155 mg, 0.344 mmol) obtained in Example 85, 3-pyridinemethanol (40 μl, 0.413 mmol) and p-toluenesulfonic acid dihydrate (98 mg, 0.516 mmol) was heated to reflux for 2 hours while distilling off water. The reaction solution was returned to room temperature, subsequently saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, subsequently dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to flash silica gel column chromatography, and the fraction obtained from an elution with 70% ethyl acetate/hexane was concentrated under reduced pressure. Ether was added to the resulting concentration residue, and the solid thus precipitated was collected by filtration, to obtain the title compound (46 mg, 0.085 mmol, 25%) as a white powder.

Workup

  1. temperatureto reflux for 2 hours
  2. distillationwhile distilling off water
  3. customwas returned to room temperature
  4. additionsubsequently saturated aqueous sodium hydrogencarbonate was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialsubsequently dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. concentrationThe resulting concentration residue
  11. customthe fraction obtained from an elution with 70% ethyl acetate/hexane
  12. concentrationwas concentrated under reduced pressure
  13. additionEther was added to the resulting concentration residue
  14. customthe solid thus precipitated
  15. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-d6ac84d8ab9c4b5c8ce6e32c23684848
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

Loading…