Preparation method of trifluridine

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...

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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 slightly higher, very volatile, and troublesome to operate. In comparison, route ② is not as simple and convenient as route ③, and the yield is basically the same, but the cost is very high

[0010] The main problem of route ③ is that the yield is low. Even if TLC monitors that the reaction substrate is not fully reacted and then adds reagents to continue the reaction, the yield of the final product is not high, and the post-treatment adopts the method of passing through a silica gel column. Difficult to operate in industrial production

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