Preparation method of trifluridine

A technology of trifluridine and deoxyuridine, which is applied in the field of preparation and preparation of trifluridine, can solve the problems of low product yield, long reaction route, complicated operation, etc., achieve high purity, short reaction time, Simple operation effect

Active Publication Date: 2015-07-08
SHANDONG CHENGCHUANG BLUE OCEAN PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Route ① The reaction route is relatively long. After three-step reaction, there are many kinds of reagents and solvents used, the operation is more complicated, and the yield is lower;
[0009] Route ② is similar to ③, and the reaction mechanism is also similar, but the cost of trifluoroiodomethane used in route ② is much higher than that of sodium trifluoromethanesulfinate in route ③, and it is a gas, which needs to be prepared into dimethyl trifluoromethanesulfinate at low temperature. Sulfoxide solution, the temperature is s

Method used

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  • Preparation method of trifluridine
  • Preparation method of trifluridine

Examples

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Effect test

Embodiment 1

[0033] Add 228g (1mol) of 2'-deoxyuridine and 492.6g (3mol) of 95% sodium trifluoromethanesulfinate into 3.99L of purified water, stir and cool down to -3°C, protect with nitrogen flow, stir to dissolve and add dropwise 386g (3mol) 70% tert-butyl hydroperoxide, the temperature control during the dropwise addition is less than 5°C, after the dropwise addition is completed, heat up to 60°C, stir and react for 2 hours, and the reaction is complete; The ester was extracted 3 times, the extracts were combined, and concentrated under reduced pressure at 50° C. to obtain 276 g of trifluridine, with a yield of 93.2% and a purity of 96.8%.

Embodiment 2

[0035] Add 456g (2mol) of 2'-deoxyuridine and 985.2g (6mol) of 95% sodium trifluoromethanesulfinate into 7.98L of purified water, stir and cool down to -3°C, protect with nitrogen flow, stir to dissolve and add dropwise 772g (6mol) 70% tert-butyl hydroperoxide, temperature control during the dropwise addition is less than 5°C, after the dropwise addition, heat up to 60°C, stir and react for 2 hours, the reaction is complete; drop to room temperature, add 8L ethyl acetate The ester was extracted 3 times, the extracts were combined, and concentrated under reduced pressure at 50° C. to obtain 558 g of trifluridine, with a yield of 94.3% and a purity of 97.2%.

Embodiment 3

[0037] Add 1.14kg (5mol) of 2'-deoxyuridine and 2.46kg (15mol) of 95% sodium trifluoromethanesulfinate into 19.95kg of purified water, stir and cool down to -5°C, protect with nitrogen flow, stir and dissolve, then drop Add 2.12kg (16.5mol) of 70% tert-butyl hydroperoxide, and control the temperature during the dropwise addition to less than 5°C. After the dropwise addition, heat up to 65°C, stir and react for 3 hours, and the reaction is complete; 18 kg of ethyl acetate was extracted three times, the combined extracts were concentrated under reduced pressure at 50° C. to obtain 1.36 kg of trifluridine, yield: 91.9%, purity: 96.4%.

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Abstract

The invention discloses a preparation method of trifluridine. The method comprises the specific steps of: adding 2'-deoxyuridine and trifluoromethyl sulfinate sodium to a reaction solvent, stirring and cooling to - 5 to - 3 DEG C, introducing of nitrogen for protection, stirring to dissolve, dropwise adding tert-butyl hydroperoxide, controlling the temperature at less than 5 DEG C, heating to 60-65 DEG C for reaction, and conducting posttreatment after the reaction to obtain a finished product. The method provided by the invention has mild reaction conditions, simple operation, little side reaction, short reaction time, great reduction of feeding amount of tert-butyl hydroperoxide, great saving of the production cost, and high yield and high purity of the product, and is especially applicable to industrial production, and has significance to the quality control of medicine and clinical curative effect.

Description

technical field [0001] The invention relates to a preparation method, in particular to a preparation method of trifluridine. It belongs to the field of medical technology. Background technique [0002] Trifluridine, chemical name: 5-trifluoromethyl-2-deoxyuridine, has the strongest effect on herpes simplex virus (HSV-1 and HSV-2), and has the strongest effect on adenovirus, vaccinia virus, cytomegalovirus, Herpes zoster virus also has a certain effect, and it is effective against acyclovir-resistant herpes virus. Its triphosphate derivatives can be incorporated into DNA and compete with thymidine triphosphate to inhibit DNA polymerase. No selectivity for viral DNA and host cell DNA. It is suitable for herpes simplex keratitis, conjunctivitis and other herpetic eye diseases. The chemical structural formula is as follows: [0003] [0004] At present, there are mainly three methods for preparing trifluridine: [0005] ①Using trifluorouracil as the starting material, p...

Claims

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Application Information

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IPC IPC(8): C07H19/073C07H1/00
Inventor 宋文同吕志涛王丽姚松芝
Owner SHANDONG CHENGCHUANG BLUE OCEAN PHARM TECH CO LTD
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