新产品编号:1952697
Chemical Name: 1-[4-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]cyclopropanol
项目整合开发状态: Biological Testing
项目研究机构: Bayer (Originator)
合成路线:The cyclization of 1-(2-fluorobenzyl)pyrazolo[3,4-b]pyridine-3-carboxamidine (I) (see scheme no.28591301a,intermediate (IX)) with ethyl 2-(ethoxymethylene)cyanacetate (II) in refluxing toluene gives the pyrimidine-5-carboxylate derivative (III),which is cyclized to the target 1-hydroxycyclopropyl derivation by reaction with CH2I2 and SmI2 in hot THF.
📌 参考资料/链接：
参考文献标题:Substd.pyrazole deriv.
文献作者:Perzborn,E.; Kern,A.; Stasch,J.-P.; Straub,A.; Feurer,A.; Dembowsky,K.; Alonso-Alija,C.; Stahl,E.(Bayer AG)
参考来源:DE 19920352; WO 0066582
📄 详细内容
合成路线:The cyclization of 1-(2-fluorobenzyl)pyrazolo[3,4-b]pyridine-3-carboxamidine (I) (see scheme no.28591301a,intermediate (IX)) with ethyl 2-(ethoxymethylene)cyanacetate (II) in refluxing toluene gives the pyrimidine-5-carboxylate derivative (III),which is cyclized to the target 1-hydroxycyclopropyl derivation by reaction with CH2I2 and SmI2 in hot THF.
合成路线:The cyclization of 1-(2-fluorobenzyl)pyrazolo[3,4-b]pyridine-3-carboxamidine (I) (see scheme no.28591301a,intermediate (IX)) with phenylazomalononitrile (II) by means of NaOMe in hot DMF gives the pyrimidine (III),which is reduced with H2 over RaNi in hot DMF to yield the triaminopyrimidine (IV).The reductocondensation of (IV) with 2-(tert-butyldimethylsilyloxy)acetaldehyde (V) by means of NaBH3CN in methanol/AcOH affords the adduct (VI),which is desilylated by means of TBAF in THF to provide the 2-hydroxyethylamino derivative (VII).Finally,this compound is cyclized with aqueous glyoxal (VIII) to furnish the target tricyclic compound.
参考文献标题:Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase
文献作者:Straub,A.; Benet-Buckholz,J.; Fr鰀e,R.; Kern,A.; Kohlsdorfer,C.; Schmitt,P.; Schwarz,T.; Siefert,H.-M.; Stasch,J.-P.
参考来源:Bioorg Med Chem 2002,10(6),1711