A kind of method for preparing tegafur

Abstract

The invention relates to a method for preparing tegafur, which belongs to the field of drug synthesis. Follow the steps below: (1) Weigh 2,3-dihydrofuran and ethanol into the flask, add solvent tetrahydrofuran to it, then weigh 5-20% of the total mass of raw materials CuCl2, microwave irradiation 250W, react at 25°C for 0.6h. (2) Cool to room temperature, then add 5-fluorouracil with a molar ratio of 3:10 to 2,3-dihydrofuran, microwave irradiation 200-600W, reaction temperature 60-130°C, and react for 0.7h; After boiling the solvent, an oily substance was obtained; washed with ether to obtain a white solid, and the obtained solid was recrystallized with absolute ethanol to obtain the product. The process does not use toxic solvent chloroform, does not use high-boiling point solvents, and the one-step production cost is low. Microwave irradiation-assisted synthesis can speed up the reaction rate, and is widely used in organic substitution reactions.

Description

technical field [0001] The invention relates to a new method for preparing tegafur, which belongs to the field of drug synthesis. Background technique [0002] Tegafur is a derivative of 5-fluorouracil, which was synthesized by Hiller in the former Soviet Union in 1967 (S. A. Hiller, R. A. Zhuk, M. Yu. Lidak, et al. Substituted Uracil [P]. British Patent, 1168391(1969)). It was listed in Japan in 1974. It was successfully developed by Shandong Jinan Pharmaceutical Factory in 1979 in my country. It is currently produced in Shanghai, Shandong and other provinces and cities. Tegafur's anti-cancer effect is similar to that of 5-fluorouracil, which can be transformed into 5-fluorouracil through liver activation in vivo. Different from 5-fluorouracil, tegafur is fat-soluble, well absorbed orally, maintains a high concentration in the blood for a long time, and easily passes through the blood-brain barrier. Clinical and animal experiments have shown that tegafur has a better effe...

AI Technical Summary

Problems solved by technology

In the traditional synthesis method, in order to obtain the product, the second-step reaction needs to be continuously heated at 160°C for 5-6 hours, which has high energy consumption; 2, difficult purification and low yield: since 5-fluorouracil is a solid powder, and the reaction It needs to be carried out at high temperature (160°C), which requires the use of high boiling point solvent N,N-dimethylformamide (DMF)

However, it is difficult to completely remove it from tegafur, because DMF can form hydrogen bonds with tegafur molecules, and it is difficult to separate each other; 3. In order to separate and recycle unreacted 5-fluorouracil from tegafur , in the traditional method using the carcinogenic solvent chloroform as the extractant to separate 5-fluorouracil and tegafur

However, chloroform mainly acts on the central nervous system on the human body, has an anesthetic effect, and is harmful to the heart, liver, and kidney; it is also harmful to the environment and can cause pollution to water bodies

Therefore, using a large amount of volatile solvent chloroform, even if necessary measures are taken to reduce its volatilization, will still cause harm to human life, health and the environment; 4. Low yield