反应详情

Sodium hydride (0.4 g) was added to a solution of intermediate 1 (2.3 g) in THF (65 ml). The mixture was stirred and refluxed for 3 hours, then cooled (solution I). 1,1′-Carbonylbis-1H-imidazole (1.65 g) was added to a solution of 4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylic acid (2.42 g) in ACN (65 ml), stirred at room temperature. This mixture was stirred for 2 hours at room temperature. The solvent was evaporated. The residue was dissolved in THF (65 ml) (solution II). At room temperature, solution (II) was poured out into solution (I) and the reaction mixture was stirred for 90 minutes at room temperature. The solvent was evaporated. The residue was partitioned between DCM and water. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue was solidified in DIPE. The precipitate was filtered off and dried vacuum; 50° C.), yielding 1.58 g (33%) [1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylate (compound 6).

1. temperaturerefluxed for 3 hours
2. stirringstirred at room temperature
3. stirringThis mixture was stirred for 2 hours at room temperature
4. customThe solvent was evaporated
5. dissolutionThe residue was dissolved in THF (65 ml) (solution II)
6. additionAt room temperature, solution (II) was poured out into solution (I)
7. stirringthe reaction mixture was stirred for 90 minutes at room temperature
8. customThe solvent was evaporated
9. customThe residue was partitioned between DCM and water
10. customThe organic layer was separated
11. customdried
12. filtrationfiltered
13. customthe solvent was evaporated
14. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5)
15. customThe pure fractions were collected
16. customthe solvent was evaporated
17. filtrationThe precipitate was filtered off
18. customdried vacuum