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Method for preparing 2'-deoxyuridine

A technology of deoxyuridine and uridine, which is applied in the field of medicine, can solve the problems of high environmental and human hazards and difficult waste disposal, and achieve the effects of shortening the production cycle, reducing equipment investment, and reducing labor costs

Inactive Publication Date: 2016-11-23
SHANGHAI AMAZIN BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that the halogenated reagent used is acyl bromide, which is relatively harmful to the environment and human body, and the waste generated at the same time is difficult to handle.

Method used

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  • Method for preparing 2'-deoxyuridine
  • Method for preparing 2'-deoxyuridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1 prepares 2'-deoxyuridine shown in formula (IV) in three steps

[0028] a, Preparation of uridine dehydrate

[0029] 100 g of uridine (compound of formula I), 105 g of diphenyl carbonate, 0.5 g of sodium hydroxide and 200 ml of N,N-dimethylformamide (DMF) were incubated at 140° C. for 12 hours. Evaporate the solvent to dryness, add 200ml of a mixed solvent of methanol and ethyl acetate, keep at 60°C for 2h, keep at 4°C for 2h to crystallize, filter and dry to obtain uridine dehydrate 92g, HPLC purity 99.5%.

[0030] b, Preparation of uridine nucleoside halides

[0031] 50 g of uridine dehydrate was added to a DMF solution of 200 g of HCl, and kept at 40° C. for 14 hours. Evaporate the solvent to dryness, add 100ml of water, keep at 4°C for 2h to crystallize, filter and dry to obtain 55g of uridine nucleoside halide, HPLC purity 98.9%.

[0032] c, Preparation of 2'-deoxyuridine

[0033] Add 5 g of nickel and 200 ml of methanol to 25 g of uridine halide, f...

Embodiment 2

[0034] Example 2 One-pot preparation of 2'-deoxyuridine shown in formula (IV)

[0035] 20 g of uridine (compound of formula I), 15 g of dimethyl carbonate, 0.2 g of sodium hydroxide and 100 ml of N,N-dimethylformamide (DMF) were incubated at 140° C. for 12 hours. A solution of 50 g of HCl in DMF was added. Incubate at 40°C for 15 hours. Add 5g of nickel and 200ml of methanol, feed hydrogen to maintain the pressure of hydrogen, slowly add a certain amount of 4mol / L sodium hydroxide dropwise, and keep the temperature at 40°C for 20 hours. The liquid was evaporated to dryness, and 20 g of water was added to the solid, crystallized at 4°C, recrystallized from methanol, and dried to obtain 16.1 g of 2'-deoxyuridine (compound of formula IV), with an HPLC purity of 99.0%.

Embodiment 3 1

[0036] Example 3 One-pot method for preparing 2'-deoxyuridine (compound of formula IV)

[0037] 20 g of uridine (compound of formula I), 20 g of diethyl carbonate, 2 g of sodium bicarbonate and 100 ml of DMF were incubated at 90° C. for 3 hours. A solution of 60 g of HCl in DMF was added. Incubate at 50°C for 24 hours. Add 10g of nickel and 200ml of methanol, pass in hydrogen, keep the pressure of hydrogen, slowly add a certain amount of 4mol / L sodium hydroxide dropwise, and keep the temperature at 50°C for 5 hours. The liquid was evaporated to dryness, and 20 g of water was added to the solid, crystallized at 4°C, recrystallized from methanol, and dried to obtain 15.0 g of 2'-deoxyuridine (compound of formula IV), with an HPLC purity of 99.4%.

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Abstract

The invention discloses a method for preparing 2'-deoxyuridine shown in a preparation formula (IV) (please see the formula in the description). The method comprises the following steps that uridine shown in the formula (I) (please see the formula in the description) and a dehydrating agent are mixed in a solvent according to the following chemical equation, and uridine dehydrated matter shown in the formula (II) (please see the formula in the description) is generated under the catalyzing action of inorganic alkali; halogen hydride is added, and uridine halide shown in the formula (III) (please see the formula in the description) is generated through a halogenation reaction; hydrogen is introduced, and 2'-deoxyuridine shown in the formula (IV) is generated through a reduction reaction. According to the method for preparing 2'-deoxyuridine shown in the formula (IV), little harm is generated to the environment and the human body, and generated waste can be recycled; in addition, the one-pot preparation method is adopted, operation is easy, the labor cost is low, equipment investment is low, the production cycle is significantly shortened, and the method is suitable for industrialized mass production.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a method for preparing 2'-deoxyuridine from uridine as a raw material. Background technique [0002] 2'-Deoxyuridine, which belongs to pyrimidine deoxynucleoside, is itself a highly selective, efficient, and low-toxic antitumor drug. It is also an intermediate of the drug 2'-deoxy-5-fluoro-uridine. At present, it is mainly obtained by biosynthesis (including DNA enzymatic hydrolysis, fermentation and enzymatic method) and chemical synthesis. The existing technology of biological method is immature, and chemical method is the main preparation at present. [0003] The existing chemical preparation method is carried out by a three-step reaction, using uridine as a raw material, using propionyl bromide or acetyl bromide as a halogenating agent to simultaneously acylate protection and bromination, reductive debromination, and finally saponification and deacylation. The disadvantag...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/073C07H1/00
CPCC07H19/073C07H1/00
Inventor 于晓锋邱贵森
Owner SHANGHAI AMAZIN BIOTECHNOLOGY CO LTD
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