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A kind of preparation method of tegafur

A technology of tegafur and fluorouracil, which is applied in the field of drug synthesis, can solve problems such as harsh reaction conditions and complex protective groups, and achieve the effects of mild reaction conditions, high yield, and simple product purification methods

Inactive Publication Date: 2019-05-17
深圳万乐药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Japanese Patent Publication Sho.No.52-5518 and Japanese Patent Disclosures Sho.No.51-8282 and Sho.No.51-52182 disclose another method for synthesizing tegafur bulk drug, using 5-fluoro-urea Pyrimidine directly reacts with 2-chloro-tetrahydrofuran, 2-acyloxy-tetrahydrofuran or 2-alkoxy-tetrahydrofuran. The above synthetic methods all have technical difficulties or technical defects such as harsh reaction conditions and complicated protective groups. Therefore, tega It is meaningful work to improve the existing technology of fluorine synthesis

Method used

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  • A kind of preparation method of tegafur

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Add 100 grams (0.769 mol) of 5-fluoro-uracil, 83.5 grams (1.192 mol) of 2,3-dihydrofuran, 800 milliliters of acetonitrile, and 8.7 grams of triethylamine in the flask, cool down to 15°C, and add 148.5 grams of (1.586mol) dimethylchlorosilane, react at 16°C for 2-3 hours, after the reaction is complete, pour the reaction solution into 1000 ml of ice water, adjust the pH of the solution to 9 with sodium hydroxide, and stir at room temperature for 30 minutes , extracted twice with 300 milliliters of petroleum ether, discarded the organic phase, adjusted the pH value of the aqueous phase to 4.5 with hydrochloric acid, extracted three times with 400 milliliters of dichloromethane, dried the organic phase with anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to obtain shallow yellow solid.

[0021] The obtained light yellow solid was added to a flask, 860 ml of acetone was added, heated to dissolve at 50°C, crystallized at -20°C for 4 hours, and...

Embodiment 2

[0023] Add 100 grams (0.769 mol) of 5-fluoro-uracil, 96 grams (1.371 mol) of 2,3-dihydrofuran, 800 milliliters of acetonitrile, and 8.7 grams of triethylamine into the flask, cool down to 15°C, and add 200 grams of (2.137mol) dimethylchlorosilane, react at 18°C ​​for 2-3 hours, after the reaction is complete, pour the reaction solution into 1000 ml of ice water, adjust the pH of the solution to 9 with sodium hydroxide, and stir at room temperature for 30 minutes , extracted three times with 300 milliliters of petroleum ether, discarded the organic phase, adjusted the pH value of the aqueous phase to 4.4 with hydrochloric acid, extracted three times with 400 milliliters of dichloromethane, dried the organic phase with anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to obtain light yellow solid

[0024] The obtained light yellow solid was added to a flask, 860 ml of acetone was added, heated and dissolved at 50°C, crystallized at 0°C for 8 hours, ...

Embodiment 3

[0026] Add 100 grams (0.769 mol) of 5-fluoro-uracil, 150 grams (2.14 mol) of 2,3-dihydrofuran, 800 milliliters of acetonitrile, and 8.7 grams of triethylamine into the flask, cool down to 15°C, and add 108.5 grams of (1.16mol) dimethylchlorosilane, react at 16°C for 2-3 hours, after the reaction is complete, pour the reaction solution into 1000 ml of ice water, adjust the pH of the solution to 9 with sodium hydroxide, and stir at room temperature for 30 minutes , extracted twice with 300 milliliters of petroleum ether, discarded the organic phase, adjusted the pH value of the aqueous phase to 4.5 with hydrochloric acid, extracted three times with 400 milliliters of dichloromethane, dried the organic phase with anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to obtain shallow yellow solid.

[0027] The obtained light yellow solid was added to a flask, 860 ml of acetone was added, heated to dissolve at 50°C, crystallized at -10°C for 6 hours, and ...

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Abstract

The invention provides a preparation method of tegafur. According to the preparation method, dimethylchlorosilane is adopted for activation, and tegafur is prepared via reaction of 5-fluorouracil with 2,3-dihydrofuran; reaction conditions are mild; no high temperature or high pressure is needed; no special equipment requirement is needed; operation is simple; compound purifying is convenient; tegafur products with purity of 99.9% or higher and yield of 80% or higher are obtained; and the preparation method is suitable for industrialized production.

Description

technical field [0001] The invention relates to the field of drug synthesis methods, in particular to a preparation method of an antineoplastic drug fluorouracil derivative tegafur raw material. Background technique [0002] Tegafur (also known as Tegafur, Ftorafur, FT207), chemical name: 1-(tetrahydro-2-furyl)-5-fluoro-2,4(1H,3H)-pyrimidinedione, is a pyrimidine anticancer One of the drugs, it is the prodrug of 5-fluoro-uracil (5-Fu), which has inhibitory effect on most solid tumors, and its structural formula is as follows: [0003] [0004] Tegafur is a derivative of fluorouracil, which is gradually transformed into fluorouracil by liver activation in vivo to play an anti-tumor effect. It interferes and blocks DNA, RNA and protein synthesis in vivo, and is a cell cycle-specific drug. It is mainly used clinically to treat gastrointestinal tumors, such as gastric cancer, rectal cancer, pancreatic cancer, liver cancer, and also breast cancer. The domestic marketed prepar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D405/04
CPCC07D405/04
Inventor 刘东华于玉根吴子强袁庆熊春德苏云淡
Owner 深圳万乐药业有限公司
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