反应详情

A mixture of 5-methyl-1-(3-chlorophenyl)pyrazole-4-carboxylic acid (234 mg, 1.0 mmol) and 5 ml SOCl2 was heated to reflux for 45 min. Excess SOCl2 was removed in vacuo via codistillation with toluene. The residue was dissolved in 2mL of anhydrous THF and added dropwise over 30 minutes to a vigorously stirred 40° C. solution of guanidine hydrochloride (344 mg, 3.6 mol) in 3.25 mL 2 N NaOH and 1.9 mL THF. The resulting mixture was heated to reflux for 4 hours and then cooled. The organic solvent was removed in vacuo. The residue was diluted with 10 mL 1 N NaOH and extracted with 5×5 mL EtOAc. The combined organic layers were dried (Na2SO4) filtered and concentrated in vacuo to a white solid. This material was dissolved in 1 mL MeOH and 18.4 μL 12 N HCl was added with stirring. The solvents were removed in vacuo with toluene azeotropes and the resulting solid was stirred in 1 mL ether/acetone (1:1) and filtered to remove residual H2O. Drying under high vacuum at 40° C. afforded the desired product (20 mg, 6%).

1. temperaturewas heated
2. temperatureto reflux for 45 min
3. customExcess SOCl2 was removed in vacuo via codistillation with toluene
4. dissolutionThe residue was dissolved in 2mL of anhydrous THF
5. temperatureThe resulting mixture was heated
6. temperatureto reflux for 4 hours
7. temperaturecooled
8. customThe organic solvent was removed in vacuo
9. additionThe residue was diluted with 10 mL 1 N NaOH
10. extractionextracted with 5×5 mL EtOAc
11. dry with materialThe combined organic layers were dried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo to a white solid
14. dissolutionThis material was dissolved in 1 mL MeOH
15. addition18.4 μL 12 N HCl was added
16. customThe solvents were removed in vacuo with toluene azeotropes
17. stirringthe resulting solid was stirred in 1 mL ether/acetone (1:1)
18. filtrationfiltered
19. customto remove residual H2O
20. customDrying under high vacuum at 40° C.