Hydrochloric Acid → HCID 57870807, compound

Temperature

60 °C

To 3-amino-5-methylpicolinonitrile (9.6 g, 72 mmol) in pyridine (63 mL) was added 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (19.6 g, 80 mmol) in one portion and the resulting reaction mixture was stirred at 60° C. for overnight. Pyridine was removed in vacuo, added 2N HCl (100 mL), extracted with EtOAc (3×300 mL; Note: due to the amide presence, solubility in EtOAc is low). Combined EtOAc layers were dried (Na2SO4), evaporated to obtain 26.3 g of crude product which contained a small amount of bis-sulfonamide which was subjected to hydrolysis in THF (200 mL) with 2N NaOH (100 mL) at room temperature for 2 hours. 2 N HCl (100 mL) Was added, extracted with EtOAc (1×700 mL, 1×250 mL), combined EtOAc layers were washed with saturated NaHCO3 solution (2×250 mL), dried (Na2SO4) and evaporated to obtain 22 g of monosulfonamide. To this dioxane (350 mL), water (450 mL) (Note: requires high dilution for fast reaction) was added, followed by NaOH (30 g, 0.75 mol) and stirred under reflux for 24 hours. Dioxane was removed in vacuo and conc. HCl (75 mL) was added slowly with cooling. The resultant solid was filtered, washed with water and dried in vacuo to afford title compound (22 g, 88% for 2 steps) as light yellow solid. (M+H) Expected: 395.0; found 394.9.

1. customthe resulting reaction mixture
2. customPyridine was removed in vacuo
3. additionadded 2N HCl (100 mL)
4. extractionextracted with EtOAc (3×300 mL
5. dry with materialCombined EtOAc layers were dried (Na2SO4)
6. customevaporated
7. customto obtain 26.3 g of crude product which
8. extractionextracted with EtOAc (1×700 mL, 1×250 mL)
9. washwere washed with saturated NaHCO3 solution (2×250 mL)
10. dry with materialdried (Na2SO4)
11. customevaporated
12. customto obtain 22 g of monosulfonamide
13. stirringstirred
14. temperatureunder reflux for 24 hours
15. customDioxane was removed in vacuo and conc. HCl (75 mL)
16. additionwas added slowly
17. temperaturewith cooling
18. filtrationThe resultant solid was filtered
19. washwashed with water
20. customdried in vacuo

ORD record

ord-e99c52ed791042ca9bdc02dad3d030f4

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884110B2