CGP-29861
Chemical Name: 3-Formylrifamycin SV hydrazone with 2-amino-7-ethylperhydro-1H-pyrido[1,2-a]pyrazine; 21-Acetoxy-8-(7-ethyloctahydropyrido[1,2-a]pyrazin-2-yliminomethyl)-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-2,7-(epoxypentadeca-1,11,13-trienimino)naphtho[2,1-b]furan-1,11-dione
CAS No. 100070-82-4
项目整合开发状态: Phase I
项目研究机构: Novartis (Originator)
合成路线:The cyclization of piperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives perhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield perhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords perhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
合成路线:The cyclization of 5-ethylpiperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives 7-ethylperhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield 7-ethylperhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords 7-ethylperhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
📌 参考资料/链接：
参考文献标题:Novel polycyclic hydrazones of rifamycins,their manufacture,and their pharmaceutical compsns.for treating tuberculosis
文献作者:Traxler,P.(Novartis Corp.)
参考来源:US 4681938
📄 详细内容
合成路线:The cyclization of piperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives perhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield perhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords perhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
合成路线:The cyclization of 5-ethylpiperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives 7-ethylperhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield 7-ethylperhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords 7-ethylperhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
合成路线:This compound has been obtained by two related ways:1.By direct condensation of rifamycin S (I) with 1-(2,4,6-trimethylphenyl)piperazine (II),followed by reduction of the quinone subunit to the target hydroquinone with sodium ascorbate.2.The bromination of rifamycin S (I) with Br2/pyridine in DMF gives 3-bromorifamycin S (III),which is condensed with piperazine (II) and reduced to the target hydroquinone as before.
参考文献标题:New Rifamycins
文献作者:Traxler,P.; Vischer,W.; Zak,O.
参考来源:Drugs Fut 1988,13(9),845
合成路线:The cyclization of piperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives perhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield perhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords perhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
合成路线:The cyclization of 5-ethylpiperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives 7-ethylperhydropyrido[1,2-a]pyrazin-1-one (III),which is reduced with LiAlH4 to yield 7-ethylperhydropyrido[1,2-a]pyrazine (IV).The reaction of (IV) with NaNO2/HCl,followed by reduction with LiAlH4,affords 7-ethylperhydropyrido[1,2-a]pyrazin-2-amine (V),which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
参考文献标题:3-Formylrifamycin SV-hydrazones with diazabicycloalkyl side-chains: New rifamycins aganist tuberculosis with long plasma half-lives
文献作者:Hauffe,S.; Tosch,W.; Batt,E.; Ashtekar,D.R.; Costa-Pereira,R.; Vischer,W.; Traxler,P.; Degen,P.; Zak,O.; Imhof,P.; Gowrishankar,R.
参考来源:27th Intersci Conf Antimicrob Agents Chemother 1987,Abst 278