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【结 构 式】 
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【分子编号】65207 【品名】(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-17-furoyloxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid 【CA登记号】 |
【 分 子 式 】C26H26F2O6S 【 分 子 量 】504.5516464 【元素组成】C 61.89% H 5.19% F 7.53% O 19.03% S 6.36% |
合成路线1
该中间体在本合成路线中的序号：(IV)The starting 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid (I) is converted to the analogous carbothioic acid (II) via activation with carbonyl diimidazole, followed by reaction with hydrogen sulfide gas (1). The α-hydroxyl group of (II) is then selectively acylated with 2-furoyl chloride (III) to give the 17-furoate ester (IV) (2, 3). Finally, condensation of thioacid (IV) with bromofluoromethane under basic conditions provides the target fluoromethyl thioester (2-4).
| 【1】 Phillipps, G.H., Bain, B.M., Williamson, C., Steeples, I.P., Laing, S.B. (Glaxo Group, Ltd.). Androstane 17β-carbothioates. GB 2088877. |
| 【2】 Biggadike, K., Jones, P., Payne, J.J. (Glaxo Group, Ltd.). 17beta-Carbothioate 17alpha-arylcarbonyloxyoxy androstane derivative as anti-inflammatory agents. EP 1305330, JP 2004505990, US 6537983, US 2003045512, WO 0212266. |
| 【3】 Biggadike, K., Coote, S.J., Noga, B., Van Oort, M.M. (Glaxo Group, Ltd.). Amorphous fluticasone 2-furoate, pharmaceutical compositions thereof and its conversion to the crystalline unsolvated form. EP 1480996, JP 2005522442, US 2005152845, WO 03066655. |
| 【4】 Partridge, J.J., Walker, D.S. (SmithKline Beecham Corp.). A method for preparing fluticasone derivatives. WO 03013427. 5. Prous Science Disease Briefings: Allergic Rhinitis (online publication). Updated 2007. |
| 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) | 14476 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C21H26F2O5 | 详情 | 详情 | |
| (II) | 14481 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid | C21H26F2O4S | 详情 | 详情 | |
| (III) | 26093 | 2-Furoyl chloride | 527-69-5 | C5H3ClO2 | 详情 | 详情 |
| (IV) | 65207 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-17-furoyloxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid | C26H26F2O6S | 详情 | 详情 |