Synthesis And Development Of Flurbiprofen Axetil,Minodronic Acid Intermediates And Pharmaceutical Intermediates

Flurbiprofen axetil is the precursor drug of flurbiprofen which is a kind of non-steroidal anti-inflammatory analgesic. This paper describes a method using flurbiprofen and1-acetoxyethyl bromine as raw materials to synthesis the flurbiprofen axetil.1-acetoxy ethyl bromine was firstly synthesized from paraldehyde and acetyl bromide in anhydrous conditions. Flurbiprofen was dissolved in isopropyl alcohol and water and purified twice by recrystallization. Those two compounds were dissolved in acetone, added potassium carbonate and stirred for reaction. Finally the target compound was purified by SiO2column chromatography (petroleum ether:ethyl acetate=50:1)Minodronic acid is a new drug for osteoporosis. It can strongly inhibit the absorption function of osteoclasts and osteoclast to reduce the conversion of bone cells, can antagonize the bone marrow tumor and tumor-induced which cause osteolysis. This paper studied the preparation of the intermediate imidazo[1,2-a]pyridin-3-yl-acetic acid, and designed two synthetic routes: ethyl ester was as the raw material in the first route, condensed with acetone, bromination, cyclization with2-aminopyridine and Willgerodt-Kindler reaction to get the target compound, y-butyrolactone was used as raw material, dealed with methanol to get the hydroxy ester, the alcohol hydroxyl was oxidated to aldehyde with PCC and then brominated and cyclizated with2-aminopyridine, and then hydrolysed to get the target product in the second route.In addition, this article also describes the synthesis of some other pharmaceutical intermediates. Such as2-methyl-5-methoxy methyl benzoate,2-bromo-4-methoxy toluene,4-bromo-lH-pyridin-2-one,6-bromo-2-quinolinecarboxylic acid, triisopropyl phosphite, gefarnate and etc. Through those experiments, the synthetic routes and the quality and yield of the products were optimized by selecting the appropriate steps and conditions of the reactions.