JNJ-7706621

172935-91-0

700805-72-7

443797-96-4

The general procedure for the synthesis of 4-[[5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulfonamides from 2,6-difluorobenzohydrazide and N-[4-(aminosulfonyl)phenyl]-N'-cyanocarbamoyl phenyl ester (CAS: 700805-72-7) was as follows: a series of experiments were carried out to examine solvent and base effects on the yield of the target product as determined by HPLC. The experiments were performed as follows: N-[4-(aminosulfonyl)phenyl]-N'-cyanocarbamic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6-difluorobenzoyl hydrazine (0.3 g, 1.74 mmol) were dissolved in 15 mL of the solvent of choice, and the base of choice was added with stirring (2.08 mmol, 1.3 eq., see Table 4). The reaction mixture was heated to 80-85 °C and maintained at this temperature for 6 hours. After completion of the reaction, the mixture was cooled to 20-25 °C and sampled for HPLC analysis.The HPLC samples were prepared by diluting aliquots with acetonitrile and water (50/50) to determine the percentage conversion to 4-[[5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulphonamide and the results are presented in Table 4. Table 4: Effect of solvent and base on the yield of the target producta,b. Different amounts of isourea exchange product and decomposition were observed in all cases, except for the case where pyridine was used.c. HPLC analysis showed c-3% of the other regional isomer.d. HPLC analysis showed ~1.4% of the other regional isomer.e. The results are presented in Table 4.