新产品编号:715573
Chemical Name: 1-[5-[4-Amino-5-(3-bromophenyl)pyrido[2,3-d]pyrimidin-7-yl]pyridin-2-yl]piperidin-4-one O-(tetrahydropyran-4-yl)oxime
CAS No. 265105-63-3
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:The condensation between 3-bromobenzaldehyde (I),1-(6-morpholinyl-3-pyridinyl)ethanone (II) and malononitrile in the presence of ammonium acetate in refluxing benzene produced the bipyridyl derivative (III).Then treatment of (III) with refluxing formamide gave the title pyridopyrimidine.
合成路线:6-Chloronicotinic acid (I) was converted to the corresponding acid chloride (II) by treatment with oxalyl chloride.Condensation of acid chloride (II) with diethyl malonate in the presence of MgCl2 and Et3N produced the keto diester (III),which was further decarbethoxylated to ketone (IV) upon heating in moist DMSO.Displacement of the chloride group of (III) with 4-piperidone ethylene ketal (V) furnished the piperidinyl pyridine (VI).Knoevenagel condensation of malononitrile with 3-bromobenzaldehyde (VII) using glycine as the catalyst produced the benzylidene malononitrile (VIII).The dipyridyl derivative (IX) was obtained by condensation of ketone (VI) with dinitrile (VIII) in the presence of ammonium acetate.Cyclization of amino nitrile (IX) in hot formamide gave rise to the pyridopyrimidine system (X).Ketone (XI) was then obtained by acid hydrolysis of the ethylene ketal function of (X).Finally,condensation of ketone (XI) with 4-tetrahydropyranyloxyamine (XII) yielded the title oxime.
📌 参考资料/链接：
参考文献标题:5,7-Disubstd.-4-aminopyrido[2,3-d]pyrimidine cpds.
文献作者:Stewart,A.O.; Perner,R.J.; McKie,J.A.; Zheng,G.Z.; Grillot,A.L.; Cowart,M.D.; Bhagwat,S.S.; Lee,C.-H.(Abbott Laboratories Inc.)
参考来源:WO 0023444
📄 详细内容
合成路线:6-Chloronicotinic acid (I) was converted to the corresponding acid chloride (II) by treatment with oxalyl chloride.Condensation of acid chloride (II) with diethyl malonate in the presence of MgCl2 and Et3N produced the keto diester (III),which was further decarbethoxylated to ketone (IV) upon heating in moist DMSO.Displacement of the chloride group of (III) with 4-piperidone ethylene ketal (V) furnished the piperidinyl pyridine (VI).Knoevenagel condensation of malononitrile with 3-bromobenzaldehyde (VII) using glycine as the catalyst produced the benzylidene malononitrile (VIII).The dipyridyl derivative (IX) was obtained by condensation of ketone (VI) with dinitrile (VIII) in the presence of ammonium acetate.Cyclization of amino nitrile (IX) in hot formamide gave rise to the pyridopyrimidine system (X).Ketone (XI) was then obtained by acid hydrolysis of the ethylene ketal function of (X).Finally,condensation of ketone (XI) with 4-tetrahydropyranyloxyamine (XII) yielded the title oxime.
参考文献标题:Pyridopyrimidine analogues as novel adenosine kinase inhibitors
文献作者:Zheng,G.Z.; Lee,C.; Pratt,J.K.; Perner,R.J.; Jiang,M.Q.; Gomtsyan,A.; Matulenko,M.A.; Mao,Y.; Koenig,J.R.; Kim,K.H.; Muchmore,S.; Yu,H.; Kohlhaas,K.; Alexander,K.M.; McGaraughty,S.; Chu,K.L.; Wismer,C.T.; Mikusa,J.; et al.
参考来源:Bioorg Med Chem Lett 2001,11(16),2071