Secnidazole, RP-14539, PM-185184, Flagentyl, -Drug Synthesis Database

【结构式】

【药物名称】Secnidazole, RP-14539, PM-185184, Flagentyl

【化学名称】alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol
　　　　　　1-(2-Hydroxypropyl)-2-methyl-5-nitroimidazole
　　　　　　1-(2-Methyl-5-nitroimidazol-1-yl)-2-propanol

【CA登记号】3366-95-8

【分子式】C₇H₁₁N₃O₃

【分子量】185.18402

【开发单位】Aventis Pharma (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antitrichomonals, Treatment of Protozoal Diseases

合成路线1 合成路线2 合成路线3

合成路线1

The nitration of (I) with HNO3 and H2SO4 gives 2-methyl-4(5)-nitroimidazole (II), which is then condensed with refluxing 1-chloroisopropanol (B) or with propylene oxide in 85% formic acid (A).

参考文献中间体

【1】 Nouveaux derives de l'imidazole et compositions les contenant. FR 3270M .
【2】 Cosar, C.; Crisan, C.; Horclois, R.; Jacob, R.M.; Robert, J.; Tchelitcheff, S.; Vaupre,R.; Nitroimidazoles. Arzneim-Forsch Drug Res 1966, 16, 1, 23-29.
【3】 Hillier, K.; Secnidazole. Drugs Fut 1979, 4, 4, 280.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	24485	Propylene oxide; 2-Methyloxirane		C₃H₆O	详情	详情
(B)	33274	1-chloro-2-propanol; 1-chloroisopropanol	127-00-4	C₃H₇ClO	详情	详情
(I)	15670	2-Methylimidazole; 2-Methyl-1H-imidazole	693-98-1	C₄H₆N₂	详情	详情
(II)	33273	2-methyl-5-nitro-1H-imidazole; 2-methyl-5-nitroimidazole	696-23-1	C₄H₅N₃O₂	详情	详情

合成路线2

The condensation of (I) with propylene oxide (A) in ethanol at 20 C gives 1-(2-hydroxypropyl)-2-methylimidazole (III), which is acetylated with acetyl chloride in refluxing acetonitrile yielding the corresponding acetate (IV). The nitration of (IV) by means of HNO3 and P2O5 affords 1-(2-acetoxypropyl)-2-methyl-4-nitroimidazole (V), which is finally hydrolyzed with 4N HCl at 90 C.

参考文献中间体

【1】 Cosar, C.; Crisan, C.; Horclois, R.; Jacob, R.M.; Robert, J.; Tchelitcheff, S.; Vaupre,R.; Nitroimidazoles. Arzneim-Forsch Drug Res 1966, 16, 1, 23-29.
【2】 Jeanmart, C.; Messer, M. (Aventis Pharma SA); New process for the preparation of 5-nitroimidazole derivatives. DE 2107405; FR 2079880; GB 1278757; JP 49080066 .
【3】 Hillier, K.; Secnidazole. Drugs Fut 1979, 4, 4, 280.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	24485	Propylene oxide; 2-Methyloxirane		C₃H₆O	详情	详情
(I)	15670	2-Methylimidazole; 2-Methyl-1H-imidazole	693-98-1	C₄H₆N₂	详情	详情
(III)	33275	1-(2-methyl-1H-imidazol-1-yl)-2-propanol; 1-(2-hydroxypropyl)-2-methylimidazole		C₇H₁₂N₂O	详情	详情
(IV)	33276	1-methyl-2-(2-methyl-1H-imidazol-1-yl)ethyl acetate		C₉H₁₄N₂O₂	详情	详情
(V)	33277	1-(2-Acetoxypropyl)-2-methyl-4-nitroimidazole; 1-Methyl-2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl acetate		C₉H₁₃N₃O₄	详情	详情

合成路线3

The reaction of (I) with chloroacetone (C) by means of K2CO3 in refluxing acetone gives (2-methylimidazol-1-yl)acetone (VI), which is nitrated with HNO3 and P2O5 affording the corresponding nitro compound (VII). Finally, this product is reduced with NaBH4 in methanol at room temperature.

参考文献中间体

【1】 Cosar, C.; Crisan, C.; Horclois, R.; Jacob, R.M.; Robert, J.; Tchelitcheff, S.; Vaupre,R.; Nitroimidazoles. Arzneim-Forsch Drug Res 1966, 16, 1, 23-29.
【2】 Jeanmart, C.; Messer, M. (Aventis Pharma SA); Process for the preparation of 5-nitroimidazole derivatives. CH 513177; DE 2107423; FR 2079879; GB 1278758; NL 7101641 .
【3】 Hillier, K.; Secnidazole. Drugs Fut 1979, 4, 4, 280.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15670	2-Methylimidazole; 2-Methyl-1H-imidazole	693-98-1	C₄H₆N₂	详情	详情
(VI)	33278	(2-methylimidazol-1-yl)acetone; 1-(2-methyl-1H-imidazol-1-yl)acetone		C₇H₁₀N₂O	详情	详情
(VII)	33279	1-(2-methyl-5-nitro-1H-imidazol-1-yl)acetone		C₇H₉N₃O₃	详情	详情
(C)	15288	1-Chloroacetone; Chloroacetone	78-95-5	C₃H₅ClO	详情	详情

Extended Information