反应详情

1H-imidazole (2.72 g) was added to a solution of 6-chloro-2-[3-[4-(hydroxymethyl)-1-piperidinyl]propyl]-3(2H)-pyridazinone (2.62 g) in THF (100 ml). NaH (60%, 0.4 g) was added, under nitrogen atmosphere. The mixture was stirred for 10 minutes. 1-[(4-Amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]-1H-imidazole (2.64 g) was added and the resulting reaction mixture was stirred for 15 minutes at room temperature. The solvent was evaporated. The residue was partitioned between water and DCM. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/hexane/(CH3OH/NH3) 50/45/5). The desired fractions were collected and the solvent was evaporated. The residue was crystallized from DIPE with a drop of ACN. The precipitate was filtered off, washed and dried, yielding 1.88 g (39%) of [1-[3-(3-chloro-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate (compound 21, mp: 137° C.) In a similar way, [1-[3-(3-methyl-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]-methyl 7-amino-6-chloro-1,3-benzodioxole-4-carboxylate (compound 22) was also prepared.

1. customthe resulting reaction mixture
2. stirringwas stirred for 15 minutes at room temperature
3. customThe solvent was evaporated
4. customThe residue was partitioned between water and DCM
5. customThe organic layer was separated
6. customdried
7. filtrationfiltered
8. customthe solvent was evaporated
9. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/hexane/(CH3OH/NH3) 50/45/5)
10. customThe desired fractions were collected
11. customthe solvent was evaporated
12. customThe residue was crystallized from DIPE with a drop of ACN
13. filtrationThe precipitate was filtered off
14. washwashed
15. customdried