|
【结 构 式】 
|
【药物名称】Bermoprofen, AD-1590, Dibenon 【化学名称】2-(8-Methyl-10,11-dihydro-11-oxodibenz[b,f]oxepin-2-yl)propionic acid 【CA登记号】72619-46-6 (K salt;racemic), 72619-34-2 (racemate) 【 分 子 式 】C18H16O4 【 分 子 量 】296.32582 |
【开发单位】Dainippon Pharmaceutical (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antipyretics, Non-Opioid Analgesics, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The reaction of 2-iodo-5-methylbenzoic acid (I) with 4-hydroxyacetophenone (II) by means of K2CO3 in nitrobenzene at 150 C gives 2-(4-acetylphenoxy)-5-methylbenzoic acid (III), which by reduction with LiAlH4 in refluxing THF is converted into 2-[4-(1-hydroxyethyl)phenoxy]-5-methylbenzyl alcohol (IV). The reaction of (IV) with SOCl2 in refluxing CHCl3 affords 2-[4-(1-chloroethyl)phenoxy]-5-methylbenzyl chloride (V), which is treated with NaCN in refluxing dioxane ethanol-water yielding the dinitrile (VI). The hydrolysis of (VI) with KOH in refluxing ethanol-water gives 2-[4-[2-(carboxymethyl)-4-methylphenoxy]phenyl]propionic acid (VII), which is finally cyclized by treatment with polyphosphoric acid (PPA) at 120 C.
| 【1】 Uno, H.; Nagai, Y.; Nakamura, H.; Dibenz[b,f]oxepin and dibenzo[b,f]thiepin derivatives, process for preparation thereof, method of using the same, and compositions thereof. EP 0003893; ES 477791; JP 1393170C; JP 54122284; US 4238620 . |
| 【2】 Serradell, M.N.; Arrigoni-Martelli, E.; Castaner, J.; AD-1590. Drugs Fut 1984, 9, 6, 399. |
| 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) | 34151 | 2-iodo-5-methylbenzoic acid | 52548-14-8 | C8H7IO2 | 详情 | 详情 |
| (II) | 18123 | 1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone | 99-93-4 | C8H8O2 | 详情 | 详情 |
| (III) | 34152 | 2-(4-acetylphenoxy)-5-methylbenzoic acid | C16H14O4 | 详情 | 详情 | |
| (IV) | 34153 | 1-[4-[2-(hydroxymethyl)-4-methylphenoxy]phenyl]-1-ethanol | C16H18O3 | 详情 | 详情 | |
| (V) | 34154 | 1-[4-(1-chloroethyl)phenoxy]-2-(chloromethyl)-4-methylbenzene; 4-(1-chloroethyl)phenyl 2-(chloromethyl)-4-methylphenyl ether | C16H16Cl2O | 详情 | 详情 | |
| (VI) | 34155 | 2-[4-[4-methyl-2-(2-nitriloethyl)phenoxy]phenyl]propanenitrile | C18H16N2O | 详情 | 详情 | |
| (VII) | 34156 | 2-[4-[2-(2-hydroxy-2-oxoethyl)-4-methylphenoxy]phenyl]propionic acid | C18H18O5 | 详情 | 详情 |