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【结 构 式】 
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【药物名称】 【化学名称】2-[5-[2(E)-(N,N-Diethylcarbamoyl)-1-methylvinyl]-2-(2,6-difluorobenzyloxy)phenyl]acetic acid 【CA登记号】205317-69-7 【 分 子 式 】C23H25F2NO4 【 分 子 量 】417.4568 |
【开发单位】Novartis (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Leukotriene BLT (LTB4) Antagonists |
合成路线1
Simultaneous bromination and esterification of 2'-hydroxyphenylacetic acid (I) using tetrabutylammonium tribromide in EtOH at r.t. afforded (II), which was O-alkylated with alpha-bromo-2,6-difluorotoluene (III) in the presence of K2CO3 in refluxing acetone to yield ether (IV). Subsequent Heck olefination of (IV) with diethyl crotonamide (V) in the presence of palladium acetate and tri-o-tolylphosphine provided cinnamide (VI). The target carboxylic acid was then obtained by saponification of the ethyl ester of (VI) with NaOH.
| 【1】 Greenspan, P.D.; Fujimoto, R.A.; Marshall, P.J.; Raychaudhuri, A.; Lipson, K.E.; Zhou, H.; Doti, R.A.; Coppa, D.E.; Zhu, L.; Pelletier, R.; Uziel-Fusi, S.; Jackson, R.H.; Chin, M.H.; Kotyuk, B.L.; Fitt, J.J.; Carboxy-substituted cinnamides: A novel series of potent, orally active LTB4 receptor antagonists. J Med Chem 1999, 42, 1, 164. |
| 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) | 22322 | 2-(2-hydroxyphenyl)acetic acid | 614-75-5 | C8H8O3 | 详情 | 详情 |
| (II) | 22323 | ethyl 2-(5-bromo-2-hydroxyphenyl)acetate | C10H11BrO3 | 详情 | 详情 | |
| (III) | 22316 | 2-(bromomethyl)-1,3-difluorobenzene | 85118-00-9 | C7H5BrF2 | 详情 | 详情 |
| (IV) | 22325 | ethyl 2-[5-bromo-2-[(2,6-difluorobenzyl)oxy]phenyl]acetate | C17H15BrF2O3 | 详情 | 详情 | |
| (V) | 22326 | (E)-N,N-diethyl-2-butenamide | C8H15NO | 详情 | 详情 | |
| (VI) | 22327 | ethyl 2-[5-[(E)-3-(diethylamino)-1-methyl-3-oxo-1-propenyl]-2-[(2,6-difluorobenzyl)oxy]phenyl]acetate | C25H29F2NO4 | 详情 | 详情 |