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A kind of method of synthesizing cytidine nucleoside

A technology of cytosine nucleoside and acylcytosine, which is applied in the field of organic chemistry, can solve the problems of unsuitable industrial production, easy deliquescence of cytosine, and difficulty in obtaining it, and achieve the effects of novel design route, simple process operation, and simplified production operation

Active Publication Date: 2020-09-11
TUOXIN GROUP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this method, silicon etherified cytosine is easy to deliquescence, the raw material 1-acetyl-2,3,5-tribenzoyl ribose is not easy to obtain, and the yield of this method is low, so it cannot be produced industrially

Method used

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  • A kind of method of synthesizing cytidine nucleoside

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Experimental program
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Effect test

Embodiment 1

[0025] In a 500mL three-necked flask with a stirrer and a thermometer, add N 4 - Acetylcytosine (80g, 0.52mol), dichloroethane 300mL, trimethylsilyl acetate (10.3g, 0.078mol) was added, the reaction solution was cooled to 0-10°C, and B(C 6 f 5 ) 3 (8.0g, 0.0156mol) solution, control the temperature at 0-20°C, after the dropwise addition is completed, raise the temperature to 45-55°C, continue the heat preservation reaction, the raw materials basically disappear after HPLC detection, cool down slowly and add saturated sodium bicarbonate to neutralize, separate solution, solvent extraction, combined organic phases, dried and concentrated to obtain acyl-protected cytidine 3 oil, which was directly put into the next reaction.

[0026] Disperse the oil in the previous step in methanol, feed ammonia (60g, 3.5mol), react at 10-40°C, HPLC detects that the deprotection is complete, evaporate the reaction solution, add methanol and cool down to precipitate cytidine, use 95 % ethanol ...

Embodiment 2

[0028] In a 500mL three-necked flask with a stirrer and a thermometer, add N 4 - Acetylcytosine (80g, 0.52mol), dichloroethane 300mL, trimethylsilyl acetate (6.9g, 0.052mol) was added, the reaction solution was cooled to 0-10°C, and B(C 6 f 5 ) 3 (8.0g, 0.0156mol) solution, control the temperature at 0-20°C, after the dropwise addition is completed, raise the temperature to 45-55°C, continue the heat preservation reaction, the raw materials basically disappear after HPLC detection, cool down slowly and add saturated sodium bicarbonate to neutralize, separate solution, solvent extraction, combined organic phases, dried and concentrated to obtain acyl-protected cytidine 3 oil, which was directly put into the next reaction.

[0029] Disperse the oily substance from the previous step in 500 mL of methanol, feed ammonia gas (60 g, 3.5 mol) and react at 30 ° C. HPLC detects that the deprotection is complete. The reaction solution is evaporated to dryness. After adding methanol, th...

Embodiment 3

[0031] In a 500mL three-necked flask with a stirrer and a thermometer, add N 4 - Acetylcytosine (80g, 0.52mol), 300mL of chloroform, trimethylsilyl acetate (10.3g, 0.078mol) was added, the reaction solution was cooled to 0-10°C, and B(C 6 f 5 ) 3 (8.0g, 0.0156mol) solution, control the temperature at 0-20°C, after the dropwise addition is completed, raise the temperature to 45-55°C, continue the heat preservation reaction, the raw materials basically disappear after HPLC detection, cool down slowly and add saturated sodium bicarbonate to neutralize, separate solution, solvent extraction, combined organic phases, dried and concentrated to obtain acyl-protected cytidine 3 oil, which was directly put into the next reaction.

[0032] Disperse the oily substance from the previous step in 500 mL of methanol, feed ammonia gas (60 g, 3.5 mol) and react at 30 ° C. HPLC detects that the deprotection is complete. The reaction solution is evaporated to dryness. After adding methanol, th...

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Abstract

The invention discloses a method of synthesizing cytidine and belongs to the field of nucleoside synthesis of organic chemistry. The method comprises the following reaction steps of taking N4-acylcytosine as a raw material and trimethylsilyl acetate and B(C6F5)3 as a catalyst, performing condensation on the N4-acylcytosine, the trimethylsilyl acetate, the B(C6F5)3 and tetraacetyl ribose, and thenperforming acid or alkaline deprotection to obtain cytosine. By adopting the method, the whole process only needs two-step reaction, a great quantity of silylamine is avoided from being used to perform trimethylsilyl etherification on the N4-acetylcytosine and then perform condensation with the tetraacetyl ribose, a stannic chloride condensating agent is cancelled, the cost of the raw materials islowered, and the total yield reaches 80 percent.

Description

technical field [0001] The invention belongs to the field of organic chemistry and relates to the synthesis of pyrimidine nucleoside, in particular to a method for synthesizing cytidine nucleoside. Background technique [0002] Cytosine nucleoside, chemical name: 2-carbonyl-4-aminopyrimidine, CAS number: 65-46-3, molecular formula is C 9 h 13 N 3 o 5 , is the main base component in nucleic acid RNA, as a very important pharmaceutical intermediate, it can be used to prepare antiviral, antitumor cytarabine and citicoline and other drugs. The methods currently reported in the literature are as follows: [0003] (1) As early as 1964, Nishimara et al. proposed a new method for chemically synthesizing poaghan, that is, using silyl ether-protected N4-acetylcytosine and 1-chlorotriphenyl ribose (α and β mixture) react under heating and reflux conditions to generate mixed configuration cytidine (α configuration and β configuration), and then use the combination of recrystallizat...

Claims

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Application Information

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IPC IPC(8): C07H19/067C07H1/00
CPCC07H1/00C07H19/067
Inventor 杨西宁李涛卫涛邵春喜靳海燕张赛楠
Owner TUOXIN GROUP
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