RWJ-314313

合成路线:Mitsunobu coupling of N-Boc-3-(S)-hydroxypyrrolidine (I) with 3-bromo-2-chloro-5-hydroxypyridine (II) afforded ether (III).Subsequent introduction of the cyanophenyl group in (III) to give (V) was effected by Suzuki coupling with boronic acid (IV) in the presence of palladium catalyst.Finally,acid deprotection of the Boc group of (V) furnished the title compound.

合成路线:The compound has also been obtained by solid phase synthesis.Attachment of (S)-3-hydroxypyrrolidine (VII) to p-nitrophenylcarbonate Wang resin (VI) in the presence of diisopropylethylamine provided the resin bound pyrrolidinol (VIII).Coupling of (VIII) with 3-bromo-2-chloro-5-hydroxypyridine (II) under Mitsunobu conditions gave resin (IX).Further Suzuki coupling of (IX) with 4-cyanophenylboronic acid (IV) afforded (X).The title compound was then cleaved from the resin (X) by treatment with trifluoroacetic acid.

参考文献标题:Discovery of novel pyridyl ethers as ligand for nicotinic acetylcholine receptor
文献作者:Shank,R.; Davis,C.; Reiltz,A.; Rivero,R.; Lee,J.
参考来源:219th ACS Natl Meet (March 26 2000,San Francisco) 2000,Abst MEDI 271


合成路线:The compound has also been obtained by solid phase synthesis.Attachment of (S)-3-hydroxypyrrolidine (VII) to p-nitrophenylcarbonate Wang resin (VI) in the presence of diisopropylethylamine provided the resin bound pyrrolidinol (VIII).Coupling of (VIII) with 3-bromo-2-chloro-5-hydroxypyridine (II) under Mitsunobu conditions gave resin (IX).Further Suzuki coupling of (IX) with 4-cyanophenylboronic acid (IV) afforded (X).The title compound was then cleaved from the resin (X) by treatment with trifluoroacetic acid.
参考文献标题:Synthesis and structure-activity relationship of novel pyridyl ethers for the nicotinic acetylcholine receptor
文献作者:Lee,J.; Davis,C.B.; Rivero,R.A.; Reitz,A.B.; Shank,R.P.
参考来源:Bioorg Med Chem Lett 2000,10(10),1063