反应详情

50 mg of 3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide (compound example 11) was mixed with 0.05 ml diisopropylethylamine and 1 ml DMF. 24 mg of 4-chloro-3-sulfamoylbenzoic acid and 40 mg HATU were added and the mixture stirred at room temperature overnight. LC/MS showed completed consumption of compound II. Volatiles were evaporated under a stream of nitrogen and the crude product re-dissolved in 2 ml 5% TFA/MeOH and purified by prep HPLC (C-18 reversed phase column, water/MeOH gradient, buffered with 0.1% TFA). Alternatively a water/acetonitrile gradient, buffered with 10 mM NH4OAc can be used. Product containing fractions were filtered through a cartridge filled with cation exchange resin, rinsed with methanol, eluted with 2 M solution of ammonia in methanol and evaporated. The residue was dissolved in methanol, 1.0 equiv. aq. 1.00 N HCl were added and the title compound was isolated as the mono-HCl salt by evaporation. LC/MS (M+H)+: 752. Ret. time: 2.12 min. (Condition J); analytical HPLC Ret. time: 13.29 min (Condition K).

1. customconsumption of compound II
2. customVolatiles were evaporated under a stream of nitrogen
3. dissolutionthe crude product re-dissolved in 2 ml 5% TFA/MeOH
4. custompurified by prep HPLC (C-18 reversed phase column, water/MeOH gradient, buffered with 0.1% TFA)
5. additionProduct containing fractions
6. filtrationwere filtered through a cartridge
7. additionfilled with cation exchange resin
8. washrinsed with methanol
9. washeluted with 2 M solution of ammonia in methanol
10. customevaporated
11. dissolutionThe residue was dissolved in methanol
12. addition1.0 equiv. aq. 1.00 N HCl were added