[NH2:1][C:2]1[C:3]([C:9]#N)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][C:13]=1[C:22]([F:25])([F:24])[F:23].[OH-:26].[Na+].Cl.[OH2:29]>N1C=CC=CC=1.C1COCC1.O1CCOCC1>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([S:18]([NH:1][C:2]2[C:3]([C:9]([OH:29])=[O:26])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=2)(=[O:20])=[O:19])=[CH:14][C:13]=1[C:22]([F:25])([F:24])[F:23]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.
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