Acetic Acid → 7-Ethoxy-5-fluoromethyl-N-(2,6-dichloro-3-methylphenyl)-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide

HRID 2050765Notes

Reaction equation

HRID 2050765 reaction equation
C[Si](C)(C)[NH:3][C:4]1[C:9]([Cl:10])=[CH:8][CH:7]=[C:6]([CH3:11])[C:5]=1[Cl:12].[F:15][CH2:16][C:17]1[CH:22]=[C:21](Cl)[N:20]2[N:24]=[C:25]([S:27](Cl)(=[O:29])=[O:28])[N:26]=[C:19]2[N:18]=1.CS(C)=O.[C:35](O)(=[O:37])[CH3:36]>C(#N)C.C(Cl)Cl.O>[CH2:35]([O:37][C:21]1[N:20]2[N:24]=[C:25]([S:27]([NH:3][C:4]3[C:9]([Cl:10])=[CH:8][CH:7]=[C:6]([CH3:11])[C:5]=3[Cl:12])(=[O:29])=[O:28])[N:26]=[C:19]2[N:18]=[C:17]([CH2:16][F:15])[CH:22]=1)[CH3:36]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 679Dimethyl SulfoxideHCID 11128643N-trimethylsilyl-2,6-dichloro-3-methylanilineHCID 146234725-Fluoromethyl-7-chloro-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl chloride

Product 1

HCID 150294267-Ethoxy-5-fluoromethyl-N-(2,6-dichloro-3-methylphenyl)-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution containing 6.78 g (27.3 mmol) of N-trimethylsilyl-2,6-dichloro-3-methylaniline and 3.11 g (10.9 mmol) of 5-fluoromethyl-7-chloro-1,2,4-triazolo-[1,5-a]pyrimidine-2-sulfonyl chloride in 25 ml of dry acetonitrile was prepared and 0.15 ml (2.2 mmol) of dimethyl sulfoxide was added with stirring at ambient temperature. The mixture was allowed to react for 4 days and the resulting brown solution was diluted with 150 ml of methylene chloride, washed with water and dried over magnesium sulfate. The solvent was removed by evaporation under reduced pressure and replaced with hexane to obtain, after collection of the solids and drying, 3.7 g (80 percent of theory) of the 7-chloro analog of the title compound in about 85 percent purity. A 1.85 g (4.36 mmol) portion of this was dissolved in 25 ml of dry ethanol and the solution cooled to 0°-5° C. and a mixture of 2.54 g (7.84 mmol) of 21 weight percent sodium ethoxide in ethanol and 7 ml of ethanol was added dropwise with stirring over a 15 min. period. The mixture was allowed to react for 10 min. and then about 1 ml of acetic acid was added and the combination poured into 50 ml of cold water. The solid that formed was collected, dried, extracted with ethanol, and redried to obtain 0.95 g (50 percent of theory) of the title compound as a solid melting at 197°-200° C. The proton and fluorine nmr spectra were compatible with the assigned structure.

Workup

  1. customwas prepared
  2. customto react for 4 days
  3. washwashed with water
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed by evaporation under reduced pressure
  6. customto obtain
  7. customafter collection of the solids
  8. customdrying
  9. dissolutionA 1.85 g (4.36 mmol) portion of this was dissolved in 25 ml of dry ethanol
  10. temperaturethe solution cooled to 0°-5° C.
  11. additiona mixture of 2.54 g (7.84 mmol) of 21 weight percent sodium ethoxide in ethanol and 7 ml of ethanol
  12. additionwas added dropwise
  13. stirringwith stirring over a 15 min. period
  14. customto react for 10 min.
  15. customThe solid that formed
  16. customwas collected
  17. customdried
  18. extractionextracted with ethanol
  19. customredried

Sources & evidence

ORD record
ord-d6da77ace1ee48a2adbe0255d686b630
Source dataset
uspto-grants-1991_05
Patent number
US05015286

Reaction notes

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