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【结 构 式】 
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【分子编号】54671 【品名】N'-hydroxy-4-[(5S)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]benzenecarboximidamide 【CA登记号】 |
【 分 子 式 】C11H13N3O4 【 分 子 量 】251.24204 【元素组成】C 52.59% H 5.22% N 16.72% O 25.47% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of 4-aminobenzonitrile (I) with the chiral 2,3-epoxypropanol (II) in refluxing methanol gives 4-(2,3-dihydroxypropylamino)benzonitrile (III), which is cyclized with diethyl carbonate (IV) by means of tBu-OK at 100 C to yield the oxazolidinone (V). The reaction of the cyano group of (V) with hydroxylamine in methanol affords the N-hydroxyamidine (VI), which is cyclized with Ac2O at 120 C to provide the 1,2,4-oxadiazole (VII). The hydrolysis of the acetoxy group of (VII) with K2CO3 in refluxing methanol gives the primary alcohol (VIII), which is treated with Ms-Cl and pyridine to yield the corresponding mesylate (IX). The condensation of (IX) with 2-(1-piperazinyl)acetic acid ethyl ester (X) in refluxing acetonitrile affords the adduct (XI), which is hydrogenated with H2 over Pd/C and hydrolyzed with HOAc to obtain the benzamidine derivative (XII). Finally, this compound is acylated with methyl chloroformate (XIII) and NaOH in dichloromethane/water.
| 【1】 Gante, J.; et al.; New antithrombotic RGD-mimetics with bioavailability. Bioorg Med Chem Lett 1996, 6, 20, 2425. |
| 【2】 Gante, J.; Juraszyk, H.; Raddatz, P.; Wurziger, H.; Bernotat-Danielowski, S.; Melzer, G. (Merck Patent GmbH); Adhesion receptor antagonists. CA 2175767; DE 19516483; EP 0741133; JP 1996301857; US 6455529 . |
| 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) | 15361 | 4-Aminobenzonitrile | 873-74-5 | C7H6N2 | 详情 | 详情 |
| (II) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (III) | 54669 | 4-{[(2S)-2,3-dihydroxypropyl]amino}benzonitrile | C10H12N2O2 | 详情 | 详情 | |
| (IV) | 17470 | diethyl carbonate; diethylcarbonate | 105-58-8 | C5H10O3 | 详情 | 详情 |
| (V) | 54670 | 4-[(5S)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]benzonitrile | C11H10N2O3 | 详情 | 详情 | |
| (VI) | 54671 | N'-hydroxy-4-[(5S)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]benzenecarboximidamide | C11H13N3O4 | 详情 | 详情 | |
| (VII) | 54672 | {(5S)-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl acetate | C15H15N3O5 | 详情 | 详情 | |
| (VIII) | 54673 | (5S)-5-(hydroxymethyl)-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1,3-oxazolidin-2-one | C13H13N3O4 | 详情 | 详情 | |
| (IX) | 54674 | {(5S)-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl methanesulfonate | C14H15N3O6S | 详情 | 详情 | |
| (X) | 54675 | 1-(Ethoxycarbonylmethyl)piperazine; N-(Carboethoxymethyl)piperazine; (1-Piperazino)acetic acid ethyl ester | 40004-08-8 | C8H16N2O2 | 详情 | 详情 |
| (XI) | 54676 | ethyl 2-[4-({(5R)-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)-1-piperazinyl]acetate | C21H27N5O5 | 详情 | 详情 | |
| (XII) | 54677 | ethyl 2-{4-[((5R)-3-{4-[amino(imino)methyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]-1-piperazinyl}acetate | C19H27N5O4 | 详情 | 详情 | |
| (XIII) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |