反应详情

To a cold solution (-70° C.) of 1.23 g of 3-trityl-3H-imidazo[4,5-c]quinoline (III-1) in 25 ml of THF was added dropwise a mixture of 3 ml of 1.6M solution of n-butyl lithium in hexane and 3 ml of THF while being kept at -72°~-68° C. The mixture was stirred at the same temperature for 30 min., whereby a yellow solution of 2-lithio form (III-1') was obtained. All the 2-lithio form used in the Examples hereafter are prepared according to the same reaction conditions. To the yellow solution of the compound (III-1') was added 1.04 g of cyclopropanecarbonyl chloride all at once. The temperature of the reaction solution was gradually elevated to room temperature, and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous ammonia. The organic layer was washed with water and saturated brine, successively, and dried. The ethyl acetate was removed by evaporation, and the residue was crystallized from n-hexane--ethyl acetate to give 900 mg of the crude crystals (Ib-1). The compound (Ib-1) was deprotected by mixing with 4 ml of trifluoroacetic acid. After stirring for 30 min. at room temperature, the reaction mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was washed with water and saturated brine, and dried. The ethyl acetate was removed by evaporation, and the residue was chromatographed on a column of silica gel for purification. The fraction eluted with chloroform--methanol (30:1 v/v) was concentrated and crystallized from -hexane to give 395 mg (yield: 56%) of the titled compound (Ic-1). This was recrystallized from ethanol to give colorless crystals melting at 230° C. (dec.).

1. customwhile being kept at -72°~-68° C
2. customwhereby a yellow solution of 2-lithio form (III-1') was obtained
3. customare prepared
4. customaccording to the same reaction conditions
5. customwas gradually elevated to room temperature
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was partitioned between ethyl acetate and aqueous ammonia
8. washThe organic layer was washed with water and saturated brine
9. customsuccessively, and dried
10. customThe ethyl acetate was removed by evaporation
11. customthe residue was crystallized from n-hexane
12. customethyl acetate to give 900 mg of the crude crystals (Ib-1)
13. stirringAfter stirring for 30 min. at room temperature
14. concentrationthe reaction mixture was concentrated under reduced pressure
15. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
16. washThe organic layer was washed with water and saturated brine
17. customdried
18. customThe ethyl acetate was removed by evaporation
19. customthe residue was chromatographed on a column of silica gel for purification
20. washThe fraction eluted with chloroform--methanol (30:1 v/v)
21. concentrationwas concentrated
22. customcrystallized from -hexane