新产品编号:1965353
Chemical Name: N'-(Pyrrolo[1,2-a]quinoxalin-4-yl)pyrazine-2-carbohydrazide
项目整合开发状态: Preclinical
项目研究机构: Ist. di Ricerche Farmacol. Mario Negri (Originator)
合成路线:Clauson-Kaas reaction between 2-fluoroaniline (I) and 2,5-dimethoxytetrahydrofuran (II) in refluxing HOAc affords pyrrolic compound (III),which is then converted into cyanopyrrole derivative (IV) through a one-pot sequence involving formylation with oxalyl chloride,oximation with NH2OH.HCl and dehydration with Ac2O.Cyclization of nitrile (IV) by treatment with KOH in ethylene glycol or in tert-butyl alcohol yields quinoxalinone derivative (V),which is then transformed into the hydrazine derivative (VI) by refluxing with POCl3 and catalytic N,N-dimethylaniline followed by treatment with hydrazine in MeOH.Finally,the desired product is obtained by reaction of (VI) with pyrazinecarboxylic acid (VII) in the presence of PPh3 and 2,2'-dipyridyl disulfide (Aldrithiol-2) in CH2Cl2.
📌 参考资料/链接：
参考文献标题:Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure
文献作者:Campiani,G.; Cappelli,A.; Nacci,V.; Anzini,M.; Vomero,S.; Hamon,M.; Cagnotto,A.; Fracasso,C.; Uboldi,C.; Caccia,S.; Consolo,S.; Mennini,T.
参考来源:J Med Chem 1997,40(22),3670
📄 详细内容
合成路线:Clauson-Kaas reaction between 2-fluoroaniline (I) and 2,5-dimethoxytetrahydrofuran (II) in refluxing HOAc affords pyrrolic compound (III),which is then converted into cyanopyrrole derivative (IV) through a one-pot sequence involving formylation with oxalyl chloride,oximation with NH2OH.HCl and dehydration with Ac2O.Cyclization of nitrile (IV) by treatment with KOH in ethylene glycol or in tert-butyl alcohol yields quinoxalinone derivative (V),which is then transformed into the hydrazine derivative (VI) by refluxing with POCl3 and catalytic N,N-dimethylaniline followed by treatment with hydrazine in MeOH.Finally,the desired product is obtained by reaction of (VI) with pyrazinecarboxylic acid (VII) in the presence of PPh3 and 2,2'-dipyridyl disulfide (Aldrithiol-2) in CH2Cl2.
参考文献标题:Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors.Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent
文献作者:Campiani,G.; Aiello,F.; Fabbrini,M.; Morelli,E.; Ramunno,A.; Armaroli,S.; Nacci,V.; Garofalo,A.; Greco,G.; Novellino,E.; Maga,G.; Spadari,S.; Bergamini,A.; Ventura,L.; Bongiovanni,B.; Capozzi,M.; Bolacchi,F.; Marini,S.; et al.
参考来源:J Med Chem 2001,44(3),305