反应详情

41 mg (0.27 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were dissolved in 2 ml of DMF, 40 mg of Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to 100 mg (0.14 mmol, purity about 74%) of 2-chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), and the solution was stirred at RT overnight. In a separate flask, another 82 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 80 mg of Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to the first solution. The reaction mixture obtained was stirred at RT overnight. The mixture was then warmed to 60° C., and the reaction mixture was stirred at this temperature overnight, after which it was heated to 100° C. After stirring at 100° C. overnight, the mixture was diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 64 mg (74% of theory) of the target compound.

1. addition40 mg of Amberlyst A-21 were added
2. filtrationThe mixture was filtered off
3. stirringthe solution was stirred at RT overnight
4. addition80 mg of Amberlyst A-21 were added
5. stirringthe mixture was stirred at RT for 30 min
6. filtrationThe mixture was filtered off
7. additionadded to the first solution
8. customThe reaction mixture obtained
9. stirringwas stirred at RT overnight
10. temperatureThe mixture was then warmed to 60° C.
11. stirringthe reaction mixture was stirred at this temperature overnight
12. temperatureafter which it was heated to 100° C
13. stirringAfter stirring at 100° C. overnight
14. custompurified by preparative HPLC (acetonitrile/water+0.1% TFA)