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【结 构 式】 
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【药物名称】Etonogestrel, Org-3236 【化学名称】(17alpha)-13-Ethyl-17-hydroxy-11-methylene-18,19-dinorpregn-4-en-20-yn-3-one 【CA登记号】54048-10-1 【 分 子 式 】C22H28O2 【 分 子 量 】324.46726 |
【开发单位】Organon (Originator), Schering AG (Not Determined) 【药理作用】Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Male Contraceptives |
合成路线1
The ketalization of 11alpha-hydroxy-18-methyl-DELTA4-estrene-3,17-dione (I) with ethylene glycol (A) by means of ethyl orthoformate and p-toluene sulfonic acid gives the diketal (II), which is oxidized with CrO3 in acetone yielding the ketone (III). The Wittig reaction of (III) with triphenylmethyl-phosphonium bromide (B) by means of NaH in benzene-DMSO affords 11-methylene-18-methyl-DELTA4-estren-3,17-dione diethyleneketal (IV), which is hydrolyzed with HCl in acetone to the diketone (V). The reaction of (V) with pyrrolidine (C) in methanol gives the N-pyrrolidinyl derivative (VI), which is condensed with potassium acetylide (D) in THF yielding 17alpha-ethynyl derivative (VII). Finally, this compound is hydrolyzed with acetic acid in methanol - water.
| 【1】 Van den Broek, A.J.; Novel 11,11-alkylidene steroids. DE 2361120; ES 421253; FR 2209577; GB 1455270; JP 50029548; US 3927046 . |
| 【2】 Hillier, K.; Castaner, J.; ORG-3236. Drugs Fut 1978, 3, 9, 664. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (B) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
| (D) | 33587 | Potassium acetylide | C2HK | 详情 | 详情 | |
| (I) | 33580 | (8S,9S,10R,11R,13S,14S)-13-ethyl-11-hydroxy-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione; 11alpha-Hydroxy-18-methyl-delta4-estrene-3,17-dione | C19H26O3 | 详情 | 详情 | |
| (II) | 33581 | 11alpha-Hydroxy-18-methylestr-4-ene-3,17-dione bis(ethyleneketal) | C23H34O5 | 详情 | 详情 | |
| (III) | 33582 | 18-Methylestr-4-ene-3,11,17-trione 3,17-bis(ethyleneketal) | C23H32O5 | 详情 | 详情 | |
| (IV) | 33583 | 11-Methylene-18-methyl-delta4-estren-3,17-dione diethyleneketal; 18-Methyl-11,11-methyleneestr-4-ene-3,17-dione bis(ethyleneketal) | C24H34O4 | 详情 | 详情 | |
| (V) | 33584 | (8R,9S,10R,13S,14S)-13-ethyl-11-methylene-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C20H26O2 | 详情 | 详情 | |
| (VI) | 33585 | (8R,9S,10R,13S,14S)-13-ethyl-11-methylene-3-(1-pyrrolidinyl)-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C24H33NO | 详情 | 详情 | |
| (VII) | 33586 | (8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylene-3-(1-pyrrolidinyl)-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol | C26H35NO | 详情 | 详情 | |
| (C) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |