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【结 构 式】 
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【药物名称】Mometasone furoate, S-2640, Sch-32088, Asmanex Twisthaler, Asmanex, Nasonex, Altosone, Fulmeta, Ecotone, Ecural, Elocon 【化学名称】9,21-Dichloro-11beta,17-dihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione 17-furoate 【CA登记号】83919-23-7 【 分 子 式 】C27H30Cl2O6 【 分 子 量 】521.44255 |
【开发单位】Essex (Originator), Schering-Plough (Originator), Shionogi (Licensee) 【药理作用】Antipsoriatics, Asthma Therapy, Atopic Dermatitis, Agents for, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Antiinflammatory Drugs, Corticosteroids |
合成路线1
By esterification of mometasone (I) with 2-furoyl chloride (II) by means of TEA in dichloromethane.
| 【1】 Heggie, W.; Bandarra, J. (Hovione Sociedade Quimica SA); Process for the preparation of mometasone furoate. EP 1074558; JP 2001048897 . |
合成路线2
The reaction of 9beta,11beta-epoxy-17alpha,21-dihydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione (I) with MsCl in pyridine gives the corresponding 21-mesylate (II), which is treated with LiCl in the same solvent to yield 21-chloro-9beta,11beta-epoxy-17alpha-hydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione (III). The esterification of (III) with 2-furoyl chloride (IV) and TEA affords the expected ester (IV), which is finally treated with anhydrous HCl in acetic acid in order to open the epoxide ring to provide the target mometasone furoate. A similar reaction sequence can be performed using p-toluenesulfonyl chloride instead of mesyl chloride in the first step of the sequence.
| 【1】 Shapiro, E.L. (Schering Corp.); 3,20-Dioxo-1,4-pregnanediene-17alpha-ol 17-aromatic heterocycle carboxylates. EP 0057401; US 4472393 . |
| 【2】 Tann, C.-H.; Tsai, D.J.S.; Kwok, D.-I.; Fu, X. (Schering Corp.); Process for the preparation of 17-esters of 9alpha,21-dihalo-pregnane-11beta,17alpha-diol-20-ones. WO 9800437 . |
| 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) | 45430 | (4aS,4bS,5aS,6aS,7R,8R)-7-glycoloyl-7-hydroxy-4a,6a,8-trimethyl-5a,6,6a,7,8,9,9a,9b,10,11-decahydrocyclopenta[7,8]phenanthro[4b,5-b]oxiren-2(4aH)-one | C22H28O5 | 详情 | 详情 | |
| (II) | 45431 | (4aS,4bS,5aS,6aS,7R,8R)-7-hydroxy-4a,6a,8-trimethyl-7-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]acetyl)-5a,6,6a,7,8,9,9a,9b,10,11-decahydrocyclopenta[7,8]phenanthro[4b,5-b]oxiren-2(4aH)-one | C25H34O5S | 详情 | 详情 | |
| (III) | 45432 | (4aS,4bS,5aS,6aS,7R,8R)-7-(2-chloroacetyl)-7-hydroxy-4a,6a,8-trimethyl-5a,6,6a,7,8,9,9a,9b,10,11-decahydrocyclopenta[7,8]phenanthro[4b,5-b]oxiren-2(4aH)-one | C22H27ClO4 | 详情 | 详情 | |
| (IV) | 26093 | 2-Furoyl chloride | 527-69-5 | C5H3ClO2 | 详情 | 详情 |
| (V) | 45433 | (4aS,4bS,5aS,6aS,7R,8R)-7-(2-chloroacetyl)-4a,6a,8-trimethyl-2-oxo-2,4a,5a,6,6a,7,8,9,9a,9b,10,11-dodecahydrocyclopenta[7,8]phenanthro[4b,5-b]oxiren-7-yl 2-furoate | 103213-32-7 | C27H29ClO6 | 详情 | 详情 |
合成路线3
The esterification of 21-chloro-17alpha-hydroxy-16alpha-methyl-1,4,9(11)-pregnatriene-3,20-dione (I) with 2-furoyl chloride (II) by means of TEA gives the corresponding ester (III), which is then treated with HClO4 and 1,3-dichloro-5,5-dimethylhydantoin (DDH) in THF/water in order to add Cl-OH to the 9(11)-double bond of ester (III).
| 【1】 Shapiro, E.L. (Schering Corp.); 3,20-Dioxo-1,4-pregnanediene-17alpha-ol 17-aromatic heterocycle carboxylates. EP 0057401; US 4472393 . |
| 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) | 45434 | (10R,13S,16R,17R)-17-(2-chloroacetyl)-17-hydroxy-10,13,16-trimethyl-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | C22H27ClO3 | 详情 | 详情 | |
| (II) | 26093 | 2-Furoyl chloride | 527-69-5 | C5H3ClO2 | 详情 | 详情 |
| (III) | 45435 | (10R,13S,16R,17R)-17-(2-chloroacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl 2-furoate | 83880-65-3 | C27H29ClO5 | 详情 | 详情 |