To provide a method for easily producing anabaseine derivatives useful as a class of nicotinic receptor binding agents for use in treating Alzheimer diseases by using an easily obtainable raw material.
This method is conducted as follows: reacting a sodium salt of δ-valerolactone, obtained by reacting sodium hydride with δ-valerolactone in tetrahydrofuran, with a substituted ethyl nicotinate derivative at 15 to 35°C to obtain the Claisen product sodium 3-nicotinoyl-2-tetrahydropyranone enolate derivative, of formula II; heating the compound of formula II with concentrated HCl (e.g. for 1 hr. at 110°C) to produce 3-(5-chloro-1-pentanon-1-yl) pyridine derivative, of formula III; dissolving the compound in ethanol and then heating (e.g. at 115 to 125°C for 4 to 6 hrs.) it with an ethanolic ammonia solution in a sealed container to produce a compound of formula Ia; and dissolving the compound of formula Ia in isopropanol and then heating it with 6N HCl to produce a compound of formula Ib.
DAI NIYUIEN
INDERIJITO SHIZU
RONARUDO JII MIKETEISHIYU
