|
【结 构 式】 
|
【药物名称】Zoliprofen, 156-S, 480156-S 【化学名称】alpha-Methyl-4-(2-thiazolyloxy)benzeneacetic acid 【CA登记号】56355-17-0 【 分 子 式 】C12H11NO3S 【 分 子 量 】249.29037 |
【开发单位】Shionogi (Originator) 【药理作用】Non-Steroidal Antiinflammatory Drugs |
合成路线1
The esterification of 4-hydroxyphenylacetic acid (I) with isopropanol and H2SO4 gives the corresponding isopropyl ester (II), which is then cyclocondensed with 1-isobutoxy-2-chloroethyl isothiocyanate (III) by means of K2CO3 in acetone yielding isopropyl 2-[4-(4-isobutoxy-2-thiazolin-2-yloxy) phenyl]acetate (IV). Elimination of isobutanol from (IV) by means of p-toluenesulfonic acid in hot DMF affords isopropyl 2-[4-(2-thiazolyloxy)phenyl] acetate (V), which is methylated with methyl bromide and KOH in DMF giving isopropyl 2-[4-(2-thiazo)yloxy)phenyl]propionate (VI). Finally, this compound is hydrolyzed with NaOH in aqueous methanol.
| 【1】 Hamada, Y.; Ando, S. (Shionogi & Co. Ltd.); Improved process for the production of 2-(4-(2-thiazolyloxy)phenyl)propionic acid. CA 1188699; EP 0088008; JP 58148870 . |
| 【2】 Castaner, J.; Serradell, M.N.; Arrigoni-Martelli, E.; 480156-S. Drugs Fut 1985, 10, 1, 37. |
| 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) | 19250 | 2-propanol | 67-63-0 | C3H8O | 详情 | 详情 |
| (I) | 18430 | 2-(4-Hydroxyphenyl)acetic acid; 4-Hydroxyphenylacetic acid | 156-38-7 | C8H8O3 | 详情 | 详情 |
| (II) | 28901 | isopropyl 2-(4-hydroxyphenyl)acetate | C11H14O3 | 详情 | 详情 | |
| (III) | 28902 | 1-(2-chloro-1-isothiocyanatoethoxy)butane | C7H12ClNOS | 详情 | 详情 | |
| (IV) | 28903 | isopropyl 2-[4-[(4-butoxy-1,3-thiazol-2-yl)oxy]phenyl]acetate | C18H23NO4S | 详情 | 详情 | |
| (V) | 28904 | isopropyl 2-[4-(1,3-thiazol-2-yloxy)phenyl]acetate | C14H15NO3S | 详情 | 详情 | |
| (VI) | 28905 | isopropyl 2-[4-(1,3-thiazol-2-yloxy)phenyl]propanoate | C15H17NO3S | 详情 | 详情 |
合成路线2
The condensation of 2-chlorothiazole (VII) with isopropyl 2-(4-hydroxyphenyl)propionate (VIII) by means of K2CO3 in DMF at 150 C gives (VI), previously obtained.
| 【1】 Maeda, R.; Hirose, K. (Shionogi & Co. Ltd.); Thiazole derivatives and the production thereof. CA 1051906; FR 2248835; GB 1481465 . |
| 【2】 Castaner, J.; Serradell, M.N.; Arrigoni-Martelli, E.; 480156-S. Drugs Fut 1985, 10, 1, 37. |