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【结 构 式】 
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【分子编号】62354 【品名】 【CA登记号】 |
【 分 子 式 】C18H19N3O4 【 分 子 量 】341.36668 【元素组成】C 63.33% H 5.61% N 12.31% O 18.75% |
合成路线1
该中间体在本合成路线中的序号：(VI)In a different method, acetylation of 3-amino-1,2-propanediol (I) yields the amide diol (II). Ketalization of cyclohexanone (III) with diol (II) furnishes the spiro dioxolane (IV). The acetamide function of (IV) is then hydrolyzed to amine (V) employing aqueous hydrazine. Amine (V) is condensed with N,N'-di-(carbobenzoxy)-N''-(trifluoromethylsulfonyl)guanidine (VI) to produce the protected guanidine (VII). The N-carbobenzoxy groups of (VII) are finally removed by hydrogenolysis over Pd/C. Alternatively, amine (V) is condensed with cyanogen bromide to produce the cyanamide (VIII). Then, reaction of cyanamide (VIII) with ammonium chloride in aqueous ammonia furnishes the title guanidine compound
| 【1】 Xian, M.; Li, X.; Tang, X.; Chen, X.; Zheng, Z.; Galligan, J.J.; Kreulen, D.L.; Wang, P.G.; N-Hydroxyl derivatives of guanidine based drugs as enzymatic NO donors. Bioorg Med Chem Lett 2001, 11, 17, 2377. |
| 【2】 Xiao, J.-H.; et al.; Endogenous retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers are the major functional forms regulating retinoid-responsive elements in adult human keratinocytes. Binding of ligands to RAR only is sufficient for RAR.RXR heterodimers to co. J Biol Chem 1995, 270, 7, 3001. |
| 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) | 12979 | 3-Amino-1,2-propanediol；3-aminopropane-1,2-diol | 616-30-8 | C3H9NO2 | 详情 | 详情 |
| (II) | 62352 | N-(2,3-dihydroxypropyl)acetamide | C5H11NO3 | 详情 | 详情 | |
| (III) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (IV) | 62353 | N-(1,4-dioxaspiro[4.5]dec-2-ylmethyl)acetamide | C11H19NO3 | 详情 | 详情 | |
| (V) | 62351 | 1,4-dioxaspiro[4.5]dec-2-ylmethanamine; 1,4-dioxaspiro[4.5]dec-2-ylmethylamine | C9H17NO2 | 详情 | 详情 | |
| (VI) | 62354 | C18H19N3O4 | 详情 | 详情 | ||
| (VII) | 62356 | benzyl (Z)-{[(benzyloxy)carbonyl]amino}[(1,4-dioxaspiro[4.5]dec-2-ylmethyl)amino]methylidenecarbamate | C26H31N3O6 | 详情 | 详情 | |
| (VIII) | 62355 | 1,4-dioxaspiro[4.5]dec-2-ylmethylcyanamide | C10H16N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Condensation of benzoyl chloride (I) with ammonium thiocyanate in boiling acetone produces benzoyl isothiocyanate (II). This is then coupled with the known 3-amino-5-phenyl-1,2,4-thiadiazole (III) to afford the N-benzoyl thiourea (IV) (1). Finally, hydrolysis of (IV) under alkaline conditions gives rise to the target thiadiazolyl thiourea
| 【1】 Kurzer, F.; 1,2,4-Thiadiazolylureas. A postcript to the oxidative cyclisation of thionoamidines. J Chem Soc - Perkins Trans I 1985, 2, 311. |
| 【2】 Camden, J.B. (The Procter & Gamble Co.); Thiadiazolyl urea or thiourea derivs. for antiviral treatment. JP 2002540156; US 6258831; WO 0057878 . |
| 【3】 Agyin, J.K. (The Procter & Gamble Co.); Process for the preparation of 1,2,4-thiadiazoles. US 6297384 . |
| 【4】 Camden, J.B. (The Procter & Gamble Co.); Viral treatment. JP 2002540150; US 6245788; WO 0057869 . |
| 【5】 Camden, J.B. (The Procter & Gamble Co.); Viral treatment. US 6340696 . |