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【结 构 式】 
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【分子编号】62521 【品名】{(2R,3S,5S)-3-[(4-methylbenzoyl)oxy]-5-[8-oxo-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl]tetrahydro-2-furanyl}methyl 4-methylbenzoate 【CA登记号】 |
【 分 子 式 】C27H26N4O6 【 分 子 量 】502.5268 【元素组成】C 64.53% H 5.21% N 11.15% O 19.1% |
合成路线1
该中间体在本合成路线中的序号：(XIII)After silylation of the imidazodiazepinone (X) employing bis(trimethylsilyl)trifluoroacetamide, glycosylation with 2-deoxy-3,5-di-p-toluoyl-D-erythro-pentofuranosyl chloride (XI) leads to a mixture of glycoside anomers (XII) and (XIII), from which the desired beta-anomer (XII) can be isolated by either column chromatography or by fractional crystallization. The toluoyl ester groups of (XII) are then removed by methanolysis in the presence of NaOMe to afford (XIV). Finally, reduction of ketone (XIV) gives rise to a 60:40 mixture of the target (R)-hydroxy imidazodiazepine along with its (S)-epimer (XV), which are separated by reverse-phase preparative HPLC
| 【1】 Baker, D.C.; Putt, S.R.; A total synthesis of pentostatin, the potent inhibitor of adenosine deaminase. J Am Chem Soc 1979, 101, 20, 6127. |
| 【2】 Chan, E.; et al.; Total synthesis of (8R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol (pentostatin), the potent inhibitor of adenosine deaminase. J Org Chem 1982, 47, 18, 3457. |
| 【3】 Baker, D.C.; Putt, S.R. (Pfizer Inc.); Imidazole cpds., methods for their production and conversion of said cpds. into (R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazol[4,5-d][1,3]diazepin-8-ol. US 4195176 . |
| 【4】 Baker, D.C.; Putt, S.R. (Pfizer Inc.); 2-Amino-1-(5-amino-1H-imidazol-4-yl)ethanone and method of preparation. DE 2835144; ES 472478; ES 479618; GB 2005661; GB 2013680; US 4117229 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 40806 | 6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one | C6H6N4O | 详情 | 详情 | |
| (XI) | 37194 | (2R,3S)-5-Chloro-2-[[(4-methylbenzoyl)oxy]methyl]tetrahydro-3-furanyl 4-methylbenzoate | 4330-21-6 | C21H21ClO5 | 详情 | 详情 |
| (XII) | 62522 | {(2R,3S,5R)-3-[(4-methylbenzoyl)oxy]-5-[8-oxo-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C27H26N4O6 | 详情 | 详情 | |
| (XIII) | 62521 | {(2R,3S,5S)-3-[(4-methylbenzoyl)oxy]-5-[8-oxo-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C27H26N4O6 | 详情 | 详情 | |
| (XIV) | 62523 | 3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one | C11H14N4O4 | 详情 | 详情 | |
| (XV) | 62524 | (8S)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol | C11H16N4O4 | 详情 | 详情 |