新产品编号:95429
Chemical Name: 3-[4-(5-Methyl-2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidin-1-ylmethyl]benzonitrile
CAS No. 164393-22-0
项目整合开发状态: Preclinical
项目研究机构: Merck Sharp & Dohme (Originator)
合成路线:Condensation of 4-amino-1-benzylpiperidine (I) with benzoyl isocyanate gave the benzoyl urea (II),which was subsequently hydrolyzed to urea (III) with NaOH in aqueous methanol.Then,condensation of (III) with 2-hydroxypropiophenone (IV) in the presence of trifluoroacetic acid afforded a mixture of minor amounts of the required imidazolone (V) along with the major undesired regioisomer (VI).
合成路线:Aminopiperidine (I) was alkylated with 2-bromopropiophenone (VII),and the resulting unstable aminoketone (VIII) was treated with benzoyl isocyanate to produce the benzoyl urea (IX).Cyclization of (IX),followed by benzoyl group cleavage upon treatment with methanolic NaOMe gave the hydroxy imidazolinone (X).This was dehydrated to the imidazolone (V) by means of trifluoroacetic acid.The intermediate (V) was debenzylated to (XII) by reaction with 1-chloroethyl chloroformate,followed by treatment of the resulting (1-chloroethyl) carbamate (XI) with boiling MeOH.The debenzylated piperidine (XII) was finally alkylated with alpha-bromo-m-tolunitrile (XIII) to give the target m-cyanobenzyl derivative.
📌 参考资料/链接：
参考文献标题:Imidazolone and oxazolone derivs.as dopamine antagonists
文献作者:Carling,W.R.; Moore,K.W.(Merck Sharp & Dohme Ltd.)
参考来源:EP 0719264; JP 1997504272; US 5698573; WO 9507904
📄 详细内容
合成路线:Condensation of 4-amino-1-benzylpiperidine (I) with benzoyl isocyanate gave the benzoyl urea (II),which was subsequently hydrolyzed to urea (III) with NaOH in aqueous methanol.Then,condensation of (III) with 2-hydroxypropiophenone (IV) in the presence of trifluoroacetic acid afforded a mixture of minor amounts of the required imidazolone (V) along with the major undesired regioisomer (VI).
合成路线:Aminopiperidine (I) was alkylated with 2-bromopropiophenone (VII),and the resulting unstable aminoketone (VIII) was treated with benzoyl isocyanate to produce the benzoyl urea (IX).Cyclization of (IX),followed by benzoyl group cleavage upon treatment with methanolic NaOMe gave the hydroxy imidazolinone (X).This was dehydrated to the imidazolone (V) by means of trifluoroacetic acid.The intermediate (V) was debenzylated to (XII) by reaction with 1-chloroethyl chloroformate,followed by treatment of the resulting (1-chloroethyl) carbamate (XI) with boiling MeOH.The debenzylated piperidine (XII) was finally alkylated with alpha-bromo-m-tolunitrile (XIII) to give the target m-cyanobenzyl derivative.
参考文献标题:1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1,3-dihydroimidazol-2-one: A selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels
文献作者:Carling,R.W.; Moore,K.W.; Moyes,C.R.; Jones,E.A.; Bonner,K.; Emms,F.; Marwood,R.; Patel,S.; Fletcher,A.E.; Beer,M.; Sohal,B.; Pike,A.; Leeson,P.D.
参考来源:J Med Chem 1999,42(14),2706