Ammonia → HCID 58243598, compound

HRID 389147Notes

Reaction equation

HRID 389147 reaction equation
[CH3:1][C:2]([C:17]1[N:21]([CH3:22])[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]([F:32])([F:31])[F:30])=[N:19][N:18]=1)([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][C:6]=1[C:14]([NH2:16])=[O:15])[CH3:3].O.C(=O)(O)[O-].[Na+].[NH3:39].[CH3:40][C:41]([N:43](C)C)=[O:42]>C(O)C>[C:9]([C:8]1[CH:12]=[CH:13][C:5]([O:4][C:2]([CH3:1])([C:17]2[N:21]([CH3:22])[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:31])([F:32])[F:30])=[N:19][N:18]=2)[CH3:3])=[C:6]([C:14]2[O:15][N:39]=[C:40]([C:41]([NH2:43])=[O:42])[N:16]=2)[CH:7]=1)(=[O:10])[NH2:11]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 962Water3×HCID 31374DimethylacetamideHCID 516892Sodium BicarbonateHCID 58244183HCID 58244183, compound

Product 1

HCID 58243598HCID 58243598, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 2-oxyiminooxalate (298 mg) was added to the reaction solution B obtained in Example 55 (1), followed by stirring overnight. Water and saturated aqueous sodium bicarbonate were added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (after washing with ethyl acetate, chloroform-methanol=95:1) to obtain a white solid. The resulting solid was dissolved in dimethylacetamide (10 ml), followed by stirring at 150° C. for 8 hours. The reaction solution was cooled to room temperature and water was added thereto, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1 to 100:3) to obtain a white solid. The resulting solid was dissolved in ethanol (5 ml) and an aqueous ammonia solution (1 ml) was added thereto, followed by stirring for 30 minutes. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (chloroform:methanol=10:1). The resulting solid was washed with diisopropylether to obtain, as a white solid, 5-[5-carbamoyl-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl-1,2,4-oxadiazole-3-carboxamide (36 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (after washing with ethyl acetate, chloroform-methanol=95:1)
  5. customto obtain a white solid
  6. stirringby stirring at 150° C. for 8 hours
  7. extractionfollowed by extraction with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1 to 100:3)
  11. customto obtain a white solid
  12. stirringby stirring for 30 minutes
  13. extractionfollowed by extraction with ethyl acetate
  14. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting residue was purified by silica gel chromatography (chloroform:methanol=10:1)
  17. washThe resulting solid was washed with diisopropylether

Sources & evidence

ORD record
ord-bce8404ee016484ca95b5f2da692f768
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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