L-697661
3-[(4,7-二氯-1,3-苯氧佐-2-基)甲基氨基]-5-乙基-6-甲基-1H-吡啶-2-1Chemical Name: 3-(4,7-Dichlorobenzoxazol-2-ylmethylamino)-5-ethyl-6-methylpyridin-2(1H)-one
CAS No. 135525-78-9
项目整合开发状态: Phase II
项目研究机构: Merck Sharp & Dohme (Originator)
合成路线:L-697,661 was prepared via a convergent route:Formylation of 2-pentanone (I) with ethyl formate and sodium methoxide gave the ketoaldehyde sodium salt (II).When a mixture of anhydrous diethyl ether and absolute ethanol,6:1 v/v,was used as solvent,the desired regioisomer precipitated out of solution.Treatment of ethyl nitroacetate (III) with ethanol saturated with ammonia provided nitroacetamide ammonium salt (IV).The nitroacetamide was then condensed with (II) in an aqueous solution of piperidinium acetate to afford the 3-nitropyridinone (V).Catalytic reduction of (V) provided the 3-aminopyridinone (VI).Treatment of chloroacetonitrile (VII) with hydrogen chloride and absolute ethanol gave ethyl chloroiminoacetate hydrochloride (VIII).Nitration of 2,4-dichlorophenol (IX),followed by catalytic reduction of the resultant product,led to the aminophenol (X).Coupling of (X) with (VIII) yielded the chloromethylbenzoxazole (XI),which was converted to the corresponding iodomethyl derivative (XII).Alkylation of the 3-aminopyridinone (VI) with the iodomethylbenzoxazole (XII) furnished L-697,661.
📌 参考资料/链接：
参考文献标题:2-Pyridinone derivatives: A new class of nonnucleoside,HIV-1-specific reverse transcriptase inhibitors
文献作者:Saari,W.S.; Hoffman,J.M.; Wai,J.S.; Fisher,T.E.; Rooney,C.S.; Smith,A.M.; Thomas,C.M.; Goldman,M.E.; O'Brien,J.A.; Nunberg,J.H.; et al.
参考来源:J Med Chem 1991,34(9),2922
📄 详细内容
合成路线:L-697,661 was prepared via a convergent route:Formylation of 2-pentanone (I) with ethyl formate and sodium methoxide gave the ketoaldehyde sodium salt (II).When a mixture of anhydrous diethyl ether and absolute ethanol,6:1 v/v,was used as solvent,the desired regioisomer precipitated out of solution.Treatment of ethyl nitroacetate (III) with ethanol saturated with ammonia provided nitroacetamide ammonium salt (IV).The nitroacetamide was then condensed with (II) in an aqueous solution of piperidinium acetate to afford the 3-nitropyridinone (V).Catalytic reduction of (V) provided the 3-aminopyridinone (VI).Treatment of chloroacetonitrile (VII) with hydrogen chloride and absolute ethanol gave ethyl chloroiminoacetate hydrochloride (VIII).Nitration of 2,4-dichlorophenol (IX),followed by catalytic reduction of the resultant product,led to the aminophenol (X).Coupling of (X) with (VIII) yielded the chloromethylbenzoxazole (XI),which was converted to the corresponding iodomethyl derivative (XII).Alkylation of the 3-aminopyridinone (VI) with the iodomethylbenzoxazole (XII) furnished L-697,661.
参考文献标题:L-697,661
文献作者:Goldmann,M.E.; Wai,J.S.
参考来源:Drugs Fut 1992,17(4),283
产品链接: CAS No. 135525-78-9››