反应详情

A mixture of 6-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one (3.6 g), prepared as described in EP-A-0,353,821, 5-fluoro-1-(4-piperidinyl)-1H-indole (3.3 g), prepared according to the procedure described in Synthetic Communications, 18 (3), 265-273 (1988), sodium carbonate (1 g), potassium iodide (catalytic quantity) and sodium hydrogen carbonate (2 g) in 4-methyl-2-pentanone (150 ml) and 2-ethoxyethanol (50 ml) was stirred and refluxed overnight. The mixture was filtered and the filtrate was washed with water. The organic layer was separated, dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 95/5). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from DIPE/CH3CN. The precipitate was filtered off, dried and purified by high-performance liquid chromatography over RP-18 (eluent: (0.5% NH4OAc in H2O)/CH3OH/THF 50/40/10). The pure fractions were collected and the solvent was evaporated, yielding 1.37 g (20%) 6-[2-[4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl]-ethyl]-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one (compound 8; mp. 194.1° C.).

1. customprepared
2. customprepared
3. temperaturerefluxed overnight
4. filtrationThe mixture was filtered
5. washthe filtrate was washed with water
6. customThe organic layer was separated
7. customdried
8. filtrationfiltered
9. customthe solvent evaporated
10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 95/5)
11. customThe pure fractions were collected
12. customthe solvent was evaporated
13. customThe residue was crystallized from DIPE/CH3CN
14. filtrationThe precipitate was filtered off
15. customdried
16. custompurified by high-performance liquid chromatography over RP-18 (eluent: (0.5% NH4OAc in H2O)/CH3OH/THF 50/40/10)
17. customThe pure fractions were collected
18. customthe solvent was evaporated