Thionyl Chloride → 4-Amino-5-chloro-N-(1,2-diethyl-4-pyrazolidinyl)-2-methoxy-benzamide

HRID 1706401Notes

Reaction equation

HRID 1706401 reaction equation
S(Cl)(Cl)=O.C([NH:8][C:9]1[C:17]([Cl:18])=[CH:16][C:12]([C:13]([OH:15])=O)=[C:11]([O:19][CH3:20])[CH:10]=1)(=O)C.[NH2:21][CH:22]1[CH2:26][N:25]([CH2:27][CH3:28])[N:24]([CH2:29][CH3:30])[CH2:23]1>C(Cl)(Cl)Cl>[NH2:8][C:9]1[C:17]([Cl:18])=[CH:16][C:12]([C:13]([NH:21][CH:22]2[CH2:26][N:25]([CH2:27][CH3:28])[N:24]([CH2:29][CH3:30])[CH2:23]2)=[O:15])=[C:11]([O:19][CH3:20])[CH:10]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 5591991,2-Diethyl-4-pyrazolidinamineHCID 109884964-Acetamido-5-chloro-2-methoxybenzoic acid

Product 1

HCID 548014-Amino-5-chloro-N-(1,2-diethyl-4-pyrazolidinyl)-2-methoxy-benzamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To 75 ml. of thionyl chloride was added 12 g. (0.05 mole) of 4-acetamido-5-chloro 2-methoxy-benzoic acid and the stirred suspension refluxed one hour. The resulting solution was concentrated and 100 ml. of chloroform added to the residue which was concentrated to remove traces of thionyl chloride. The residue was dissolved in 100 ml. of chloroform and the solution added at a rapid drop to 7 g. (0.05 mole) of 4-amino-1,2-diethylpyrazolidine in 100 ml. of chloroform while stirring and cooling to 20°-25° C. with an ice bath. After 30 minutes the chloroform solution was extracted two times with 100 ml. of 3 N hydrochloric acid and the chloroform solution retained. The acid extract was boiled 10 minutes, cooled with ice, made basic with concentrated sodium hydroxide while cooling and extracted with chloroform. The chloroform was dried (sodium sulfate), concentrated and the residue crystallized from isopropyl ether-isooctane to give 3 g. of material which melted at 116°-118° C. The retained chloroform solution was extracted with dilute sodium hydroxide and concentrated. The residue was dissolved in 3 N hydrochloric acid and extracted with isopropyl ether. The acid solution was refluxed for 10 minutes, cooled with ice bath, made basic with sodium hydroxide while cooling and extracted with chloroform. The chloroform was dried (sodium sulfate) and concentrated. The residue was crystallized three times from isopropyl ether to give 0.7 g. of material which melted at 117°-119° C. A mixture melting point of both materials gave no depression of the melting point. The combined yield was 3.7 g. (23%).

Workup

  1. concentrationThe resulting solution was concentrated
  2. additionof chloroform added to the residue which
  3. concentrationwas concentrated
  4. customto remove traces of thionyl chloride
  5. dissolutionThe residue was dissolved in 100 ml
  6. additionof chloroform and the solution added at a rapid drop to 7 g
  7. temperaturecooling to 20°-25° C. with an ice bath
  8. extractionAfter 30 minutes the chloroform solution was extracted two times with 100 ml
  9. extractionThe acid extract
  10. temperaturecooled with ice
  11. temperaturewhile cooling
  12. extractionextracted with chloroform
  13. dry with materialThe chloroform was dried (sodium sulfate)
  14. concentrationconcentrated
  15. customthe residue crystallized from isopropyl ether-isooctane
  16. customto give 3 g
  17. extractionThe retained chloroform solution was extracted with dilute sodium hydroxide
  18. concentrationconcentrated
  19. dissolutionThe residue was dissolved in 3 N hydrochloric acid
  20. extractionextracted with isopropyl ether
  21. temperatureThe acid solution was refluxed for 10 minutes
  22. temperaturecooled with ice bath
  23. temperaturewhile cooling
  24. extractionextracted with chloroform
  25. dry with materialThe chloroform was dried (sodium sulfate)
  26. concentrationconcentrated
  27. customThe residue was crystallized three times from isopropyl ether
  28. customto give 0.7 g
  29. customgave no depression of the melting point

Sources & evidence

ORD record
ord-a9d09657e462455093fe322cceb1eab4
Source dataset
uspto-grants-1980_06
Patent number
US04207327

Reaction notes

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