Preparation method of tegafur

A technology of tegafur and fluorouracil, which is applied in the field of medicinal chemistry, can solve the problems of many impurities and cumbersome operations, and achieve the effects of high reaction selectivity, efficient reaction process, and increased selectivity

Active Publication Date: 2020-01-07
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] Aiming at the problems of harsh reaction conditions, cumbersome operation and many impurities in the current preparation process, the present invention provides a method suitable for indus

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  • Preparation method of tegafur
  • Preparation method of tegafur

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Embodiment 1

[0036] 5-fluorouracil (13.00g, 0.10mol), tetrahydrofuran (11.54g, 0.16mol), copper acetate (399.30mg, 2.0mmol), hydrogen peroxide solution (28.33g, 0.25mol, 30%), N,N- Add dimethylformamide (150mL) into the flask, start stirring, heat to 40°C, react for 5h, filter, pour the filtrate into a mixture of ice water (500mL) and ethyl acetate (300mL), stir for 15min, and divide liquid, and the organic phase was washed with purified water (100mL×3) and saturated brine (100mL) successively, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness under reduced pressure to obtain crude tegafur, which was recrystallized from anhydrous methanol to obtain Tegafur refined product, yield 92.35%, detected by HPLC, wherein t R =13.926min is tegafur with a purity of 99.952% and a maximum of 0.016% impurity.

Embodiment 2

[0038] 5-fluorouracil (13.00g, 0.10mol), tetrahydrofuran (7.21g, 0.10mol), copper acetate (399.30mg, 2.0mmol), hydrogen peroxide solution (28.33g, 0.25mol, 30%), N,N- Add dimethylformamide (150mL) into the flask, start stirring, heat to 40°C, react for 5h, filter, pour the filtrate into a mixture of ice water (500mL) and dichloromethane (300mL), stir for 15min and divide liquid, and the organic phase was washed with purified water (100mL×3) and saturated brine (100mL) successively, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness under reduced pressure to obtain crude tegafur, which was recrystallized from anhydrous methanol to obtain Tegafur refined product, yield 90.16%, detected by HPLC, wherein t R =13.875min is tegafur, the purity is 99.894%, and the maximum is 0.019%.

Embodiment 3

[0040] 5-fluorouracil (13.00g, 0.10mol), tetrahydrofuran (14.42g, 0.20mol), copper acetate (399.30mg, 2.0mmol), hydrogen peroxide solution (28.33g, 0.25mol, 30%), N,N- Add dimethylformamide (150mL) into the flask, start stirring, heat to 40°C, react for 5h, filter, pour the filtrate into a mixture of ice water (500mL) and ethyl acetate (300mL), stir for 15min, and divide liquid, and the organic phase was washed with purified water (100mL×3) and saturated brine (100mL) successively, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness under reduced pressure to obtain crude tegafur, which was recrystallized from anhydrous methanol to obtain Tegafur refined product, yield 91.38%, detected by HPLC, wherein t R =13.863min is tegafur, with a purity of 99.927% and a maximum of 0.016%.

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Abstract

The invention provides a preparation method of tegafur. The method mainly comprises the following steps: reacting 5-fluorouracil with tetrahydrofuran under the action of a catalyst, extracting, and recrystallizing to obtain a high-purity tegafur product. Compared with the prior art, the preparation method disclosed by the invention is simple to operate, mild in reaction condition, high in productyield, high in purity, less in pollution and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of tegafur. Background technique [0002] The compound involved in the present invention is Tegafur (also known as Tegafur, Ftorafur, FT207), chemical name: 1-(tetrahydro-2-furyl)-5-fluoro-2,4(1H,3H)-pyrimidinedione , is one of the pyrimidine anticancer drugs, it is the prodrug of 5-fluorouracil, it has inhibitory effect on most solid tumors, the structural formula is as follows: [0003] [0004] Tegafur is a derivative of 5-fluorouracil, which was first synthesized by Hiller of the former Soviet Union in 1967 and listed in Japan in 1974. It was successfully developed by Shandong Jinan Pharmaceutical Factory in 1979 in my country. The anti-cancer spectrum and curative effect of tegafur are similar to 5-fluorouracil. 450 Under the catalysis of activating enzyme, it is converted into 5-fluorouracil, and then about 10% enters the in...

Claims

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Application Information

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IPC IPC(8): C07D405/04
CPCC07D405/04
Inventor 张贵民鲍广龙张现利
Owner LUNAN PHARMA GROUP CORPORATION
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