Nevirapine, BIRG-0587, BI-RG-587, Viramune
奈韦拉平Chemical Name: 11-Cyclopropyl-4-methyl-6,11-dihydro-5H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
CAS No. 129618-40-2
项目整合开发状态: Launched-1996
项目研究机构: Boehringer Ingelheim (Originator), Nippon Boehringer Ingelheim (Licensee), Roxane (Licensee)
合成路线:The diazonium salt from 2-amino-4-methylpyridine (I) is converted to 2-hydroxy-4-methylpyridine (II),which is nitrated to give 2-hydroxy-4-methyl-3-nitropyridine (III).Conversion to 2-chloro-4-methyl-3-nitropyridine (IV) is effected with phosphorous oxychloride and phosphorous pentachloride.Reduction of (IV) with hydrogen/Raney Nickel provides 3-amino-2-chloro-4-methylpyridine (V),which is condensed with 2-chloronicotinoyl chloride to give 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (VI).Treatment with cyclopropylamine affords N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (VII),which is cyclized in the presence of sodium hydride to yield nevirapine.
📌 参考资料/链接：
参考文献标题:Inhibition of HIV-1 replication by a non-nucleoside reverse transcriptase inhibitor
文献作者:Merluzzi,V.J.; Hargrave,K.D.; Labadia,M.; Grozinger,K.G.; Skoog,M.; Wu,J.C.; Shih,C.K.; Eckner,K.; Hattox,S.E.; Adams,J.; et al.
参考来源:Science 1990,250(4986),1411-3
📄 详细内容
合成路线:The diazonium salt from 2-amino-4-methylpyridine (I) is converted to 2-hydroxy-4-methylpyridine (II),which is nitrated to give 2-hydroxy-4-methyl-3-nitropyridine (III).Conversion to 2-chloro-4-methyl-3-nitropyridine (IV) is effected with phosphorous oxychloride and phosphorous pentachloride.Reduction of (IV) with hydrogen/Raney Nickel provides 3-amino-2-chloro-4-methylpyridine (V),which is condensed with 2-chloronicotinoyl chloride to give 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (VI).Treatment with cyclopropylamine affords N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (VII),which is cyclized in the presence of sodium hydride to yield nevirapine.
参考文献标题:Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase.1.Tricyclic pyridobenzo- and dipyridodiazepinones
文献作者:Hargrave,K.D.; Proudfoot,J.R.; Grozinger,K.G.; Cullen,E.; Kapadia,S.R.; Patel,U.R.; Fuchs,V.U.; Mauldin,S.C.; Vitous,J.; Behnke,M.L.; et al.
参考来源:J Med Chem 1991,34(7),2231-41
合成路线:The diazonium salt from 2-amino-4-methylpyridine (I) is converted to 2-hydroxy-4-methylpyridine (II),which is nitrated to give 2-hydroxy-4-methyl-3-nitropyridine (III).Conversion to 2-chloro-4-methyl-3-nitropyridine (IV) is effected with phosphorous oxychloride and phosphorous pentachloride.Reduction of (IV) with hydrogen/Raney Nickel provides 3-amino-2-chloro-4-methylpyridine (V),which is condensed with 2-chloronicotinoyl chloride to give 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (VI).Treatment with cyclopropylamine affords N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (VII),which is cyclized in the presence of sodium hydride to yield nevirapine.
参考文献标题:Nevirapine
文献作者:Riska,P.S.; Johnstone,J.N.; Silverstein,H.H.; Hattox,S.E.; Norris,S.H.; St.George,R.; Grob,P.M.; Hargrave,K.D.
参考来源:Drugs Fut 1992,17(10),887
产品链接: CAS No. 129618-40-2››