Dimethylformamide → HCID 67024516, compound

HRID 389124Notes

Reaction equation

HRID 389124 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[N:15]([CH3:16])[C:14]([C:17]([CH3:29])([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])[CH3:18])=[N:13][N:12]=1)[C:5]([OH:7])=O.C1C=C[C:33]2[N:38](O)N=NC=2C=1.C[N:41]([CH:43]=[O:44])C.C([N:47](CC)CC)C>O>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:38]=[C:33]([C:43]([NH2:41])=[O:44])[N:47]=2)[CH:8]=[CH:9][C:10]=1[C:11]1[N:15]([CH3:16])[C:14]([C:17]([CH3:29])([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])[CH3:18])=[N:13][N:12]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 58244041HCID 58244041, compound

Product 1

HCID 67024516HCID 67024516, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-chloro-4-{4-methyl-5-[1-methyl-1-(2,4,6-trifluorophenoxy)ethyl]-4H-1,2,4-triazol-3-yl}benzoic acid (204 mg), WSC•monohydrochloride (138 mg), HOBt (98 mg) and DMF (4 ml) were mixed and stirred for 30 minutes. Ethyl 2-oxyiminooxalate (190 mg) and triethylamine (0.2 ml) were added thereto, followed by stirring for 2 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution and then saturated brine in this order, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was dissolved in dimethylacetamide (6 ml), followed by stirring at 130° C. for 2 hours. The reaction solution was cooled to room temperature and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water, 1M hydrochloric acid, a 1M aqueous sodium hydroxide solution and then saturated brine in that order, and was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (chloroform:methanol=100:1). The resulting residue was mixed with ethanol (5 ml) and an aqueous ammonia solution (1 ml) was added thereto, followed by stirring for 15 minutes. THF (2 ml) was added thereto, followed by stirring for 15 minutes. The reaction solution was heated until the solid was dissolved, and was then cooled to room temperature, and an aqueous ammonia solution (1 ml) was added thereto, followed by stirring for 15 minutes. Water and a 1M aqueous sodium hydroxide solution were added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, 4M hydrogen chloride-ethyl acetate (1 ml) was added thereto and the solvent was evaporated under reduced pressure. The resulting solid was washed with hexane to obtain 5-(3-chloro-4-{4-methyl-5-[1-methyl-1-(2,4,6-trifluorophenoxy)ethyl]-4H-1,2,4-triazol-3-yl}phenyl}-1,2,4-oxadiazole-3-carboxamide monohydrochloride (140 mg) as a white solid.

Workup

  1. stirringby stirring for 2 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution
  4. dry with materialsaturated brine in this order, and dried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionThe resulting residue was dissolved in dimethylacetamide (6 ml)
  7. stirringby stirring at 130° C. for 2 hours
  8. additionwater was added
  9. extractionfollowed by extraction with ethyl acetate
  10. washThe organic layer was washed with water, 1M hydrochloric acid
  11. dry with materiala 1M aqueous sodium hydroxide solution and then saturated brine in that order, and was dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel chromatography (chloroform:methanol=100:1)
  14. additionThe resulting residue was mixed with ethanol (5 ml)
  15. additionan aqueous ammonia solution (1 ml) was added
  16. stirringby stirring for 15 minutes
  17. additionTHF (2 ml) was added
  18. stirringby stirring for 15 minutes
  19. temperatureThe reaction solution was heated until the solid
  20. dissolutionwas dissolved
  21. temperaturewas then cooled to room temperature
  22. additionan aqueous ammonia solution (1 ml) was added
  23. stirringby stirring for 15 minutes
  24. additionWater and a 1M aqueous sodium hydroxide solution were added to the reaction solution
  25. extractionfollowed by extraction with ethyl acetate
  26. washThe organic layer was washed with saturated brine
  27. dry with materialdried over anhydrous magnesium sulfate
  28. customthe solvent was evaporated under reduced pressure
  29. dissolutionThe residue was dissolved in ethyl acetate
  30. addition4M hydrogen chloride-ethyl acetate (1 ml) was added
  31. customthe solvent was evaporated under reduced pressure
  32. washThe resulting solid was washed with hexane

Sources & evidence

ORD record
ord-29f9428fdcc140afb729790afbe9daab
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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