反应详情

133 mg (0.81 mmol) of N-ethyl-2,2,2-trifluoroethanamine hydrochloride were dissolved in 2 ml of DMF, 130 mg 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-ylmethyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), and the solution was stirred at RT overnight. The mixture was then warmed to 60° C. and stirred at this temperature overnight. In a separate flask, another 87 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 88 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 100° C. for 4.5 h. The mixture was then diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 37 mg (41% of theory) of the target compound.

1. addition130 mg Amberlyst A-21 were added
2. filtrationThe mixture was filtered off
3. stirringthe solution was stirred at RT overnight
4. temperatureThe mixture was then warmed to 60° C.
5. stirringstirred at this temperature overnight
6. addition88 mg of Amberlyst A-21 were added
7. stirringthe mixture was stirred at RT for 30 min
8. filtrationThe mixture was filtered off
9. additionadded to the first solution
10. customThe reaction mixture obtained
11. stirringwas stirred at 100° C. for 4.5 h
12. custompurified by preparative HPLC (acetonitrile/water+0.1% TFA)