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【结 构 式】 
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【分子编号】14484 【品名】(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-17-[[(iodomethyl)sulfanyl]carbonyl]-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate 【CA登记号】 |
【 分 子 式 】C25H31F2IO5S 【 分 子 量 】608.4854164 【元素组成】C 49.35% H 5.14% F 6.24% I 20.86% O 13.15% S 5.27% |
合成路线1
该中间体在本合成路线中的序号：(V)New methods for the synthesis of fluticasone propionate have been reported: 1) The reaction of 6alpha,9alpha-difluoro-11beta,17alpha-dihydroxy-16alpha-methyl-3-oxo and rosta-1,4-diene-17beta-carboxylic acid (I) with carbonyldiimidazole (CDI) and H2S in DMF gives the corresponding carbothioic acid (II), which is selectively acylated with propionyl chloride and triethylamine in CH2Cl2, yielding the 17alpha-propionyloxy derivative (III). The reaction of (III) with CH2BrCl and NaHCO3 in DMA affords the S-chloromethyl ester (IV), which by reaction with NaI in refluxing acetone is converted to the S-iodomethyl ester (V). Finally, this compound is treated with AgF in acetonitrile. 2) By esterification of thioacid (II) with bromofluoromethane or fluoroiodomethane by means of K2CO3 in DMF.
| 【1】 Phillips, G.H.; Bain, B.M.; Williamson, C.; Steeples, I.P.; Laing, S.B. (Glaxo Wellcome plc); Androstane 17beta-carbothioates. GB 2088877; NL 8100707; US 4335121 . |
| 【2】 Phillips, G.H.; Bailey, E.J.; Bain, B.M.; et al.; Synthesis and structure-activity relationships in a series of antiinflammatory corticosteroid analogues, halomethyl androstane-17beta-carbothioates and -17beta-carboselenoates. J Med Chem 1994, 37, 22, 3717. |
| 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) | 14478 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-(propionyloxy)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid | C24H30F2O5S | 详情 | 详情 | |
| (IV) | 14479 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-17-[[(chloromethyl)sulfanyl]carbonyl]-6,9-difluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C25H31ClF2O5S | 详情 | 详情 | |
| (V) | 14484 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-17-[[(iodomethyl)sulfanyl]carbonyl]-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C25H31F2IO5S | 详情 | 详情 |