藥物詳細合成路線
| Name | Secnidazole;RP-14539;PM-185184;Flagentyl | | Chemical Name | 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 | | CAS | 3366-95-8 | | Related CAS | | | Formula | C7H11N3O3 | | Structure |  | | Formula Weight | 185.18402 | | Stage | 上市 | | Company | Aventis Pharma (Originator) | | Activity/Mechanism | ANTIINFECTIVE THERAPY, Antitrichomonals, Treatment of Protozoal Diseases | | Syn. Route | 3 | | Route 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). | | |  | | List of intermediates | No. | | (3ar,6as)-2-oxohexahydro-2h-cyclopenta[b]furan-4-carbaldehyde | (i) | | 5-[4-[2-([[(e)-1-(6-phenyl-3-pyridinyl)ethylidene]amino]oxy)ethoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | (a) | | ethyl (1r,2s,4r)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate | (ii) | | [(1r,2s,4r)-2-isopropenyl-1-methyl-4-vinylcyclohexyl]methanol | (b) | | | Reference 1: nouveaux derives de limidazole et compositions les contenant. fr 3270m . Reference 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. Reference 3: hillier, k.; secnidazole. drugs fut 1979, 4, 4, 280. |
Route 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. | | |  | | List of intermediates | No. | | (3ar,6as)-2-oxohexahydro-2h-cyclopenta[b]furan-4-carbaldehyde | (i) | | 5-[4-[2-([[(e)-1-(6-phenyl-3-pyridinyl)ethylidene]amino]oxy)ethoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | (a) | | 1-[(1r,3s,4r)-4-(hydroxymethyl)-3-isopropenyl-4-methylcyclohexyl]-1-ethanone | (iii) | | (1r,2s,4r)-4-acetyl-2-isopropenyl-1-methylcyclohexanecarbaldehyde | (iv) | | methyl (1s,2s,3s,4r)-3-[(1s)-1-amino-2-ethylbutyl]-4-[(tert-butoxycarbonyl)amino]-2-hydroxycyclopentanecarboxylate | (v) | | | Reference 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. Reference 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 . Reference 3: hillier, k.; secnidazole. drugs fut 1979, 4, 4, 280. |
Route 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. | | |  | | List of intermediates | No. | | (2r)-2-amino-3-methyl-1-butanol; (r-(-))-valinol; d-valinol | (c) | | (3ar,6as)-2-oxohexahydro-2h-cyclopenta[b]furan-4-carbaldehyde | (i) | | methyl (1s,2s,3s,4r)-3-[(1s)-1-(acetamido)-2-ethylbutyl]-4-[(tert-butoxycarbonyl)amino]-2-hydroxycyclopentanecarboxylate | (vi) | | methyl (1s,2s,3r,4r)-3-[(1s)-1-(acetamido)-2-ethylbutyl]-4-amino-2-hydroxycyclopentanecarboxylate | (vii) | | | Reference 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. Reference 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 . Reference 3: hillier, k.; secnidazole. drugs fut 1979, 4, 4, 280. |
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來源:藥化網
作者:藥化小編
摘要:本文合成路線介紹的是藥物中文名塞克硝唑；英文名Secnidazole;RP-14539;PM-185184;Flagentyl；CAS[3366-95-8]
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