Method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine

A technology of propylmercapto and nitro, which is applied in the field of preparation of 4,6-dichloro-5-nitro-2--pyrimidine, can solve the problems of large environmental pollution, harsh reaction conditions, and low reaction yield, and achieve The effect of low operating cost and high conversion rate

Active Publication Date: 2019-09-20
ZHEJIANG UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The purpose of the present invention is to overcome the difficult problems of harsh reaction conditions, low reaction yield and large environmental pollution when preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine in the prior art, and to provide a 4 , the preparation method of 6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine

Method used

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  • Method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine
  • Method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine
  • Method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine

Examples

Experimental program
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Effect test

Embodiment 1

[0021] Add 250 milliliters of toluene in a 500 milliliter three-necked flask, add 50.0 grams of 6-hydroxyl-5-nitro-2-(propylmercapto)-4(3H)-pyrimidinone (purity: 98+%, CAS number: 145783 -12-6, alias: 4,6-dihydroxy-5-nitro-2-(propylmercapto)pyrimidine,), dissolved in toluene, cooled to 0°C, and 27.0 grams of pyrophosphorus was added dropwise within 2 hours Acyl chloride, heat up to 80°C, add 0.13 g of monoethanolamine, react for 10 hours, after the reaction, cool down to 0°C, pour into ice water, stir for 1 hour, separate layers, add 60-120 mesh neutral The silica gel was stirred for 0.5 hours, filtered, and the filtrate was rotatively evaporated at 50°C to recover toluene to obtain 45.8 grams of oily 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine, the content of which was analyzed by gas chromatography, and the content was 97.5% ( attached figure 1 ). Gas chromatograph: SHIMADZU GC-2014C. Analysis conditions: HP-1 capillary column, 15m*0.53mm, 0.15μm, initial temperatu...

Embodiment 2

[0024] Add 250 milliliters of toluene to a 500 milliliter three-necked flask, add 50.0 grams of 6-hydroxy-5-nitro-2-(propylmercapto)-4(3H)-pyrimidinone, dissolve in toluene, cool to 20°C, Add 54 grams of pyrophosphoryl chloride dropwise within 8 hours, heat up to 110°C, add 2.27 grams of diethanolamine, and react for 40 hours. After the reaction, cool down to 30°C, pour into ice water, stir for 2 hours, and separate layers. Add 60-120 mesh neutral silica gel to the upper toluene layer and stir for 1 hour, filter, the filtrate is 70°C rotary evaporation to recover toluene, and the oily product 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine 49.2 grams, content 98.1%.

Embodiment 3

[0026] Add 250 milliliters of toluene to a 500 milliliter three-necked flask, add 50.0 grams of 6-hydroxy-5-nitro-2-(propylmercapto)-4(3H)-pyrimidinone, dissolve in toluene, cool to 0°C, Add 40.0 grams of pyrophosphoryl chloride dropwise within 2 hours, heat up to 80°C, add 3.20 grams of triethanolamine, and react for 10 hours. After the reaction, cool down to 0°C, pour into ice water, stir for 1 hour, and separate layers. Add 60-120 mesh neutral silica gel to the upper toluene layer and stir for 0.5 hours, filter, and the filtrate is rotary evaporated at 50°C to recover toluene, and the oily product 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine 50.5 grams, content 98.5%.

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Abstract

The invention discloses a method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine. The method comprises the following steps: dissolving 6-hydroxy-5-nitro-2-(propylmercapto)-4-(3H)-pyrimidone into toluene, performing cooling, slowly dropping pyrophosphoryl chloride, performing heating, adding a catalyst, performing a reaction for 10-40 hours, performing cooling after the reaction is ended, pouring the reaction system into ice water, performing stirring and layering, adding neutral silica gel of 60-120 meshes into the upper toluene layer, performing stirring, performing filtration, and performing rotary evaporation on the filtrate to recycle the toluene so as to obtain the oily 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine. The method is mild in reaction condition, high in reaction yield and small in environment pollution.

Description

technical field [0001] The invention relates to the technical field of chemical industry, in particular to a preparation method of 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine. Background technique [0002] 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine is a key intermediate in the synthesis of the new anticoagulant drug ticagrelor developed by AstraZeneca. [0003] WO9905142 uses phosphine oxychloride as the chlorination reagent and solvent, and N,N-diethylaniline as the acid-binding agent to chlorinate 6-hydroxyl-5-nitro-2-(propylmercapto)-4(3H)-pyrimidine Ketone (alias: 4,6-dihydroxy-5-nitro-2-(propylmercapto)pyrimidine, both are the same substance) to prepare 4,6-dichloro-5-nitro-2-(propylmercapto)- pyrimidine. [0004] [0005] WO2011017108 adopted the same process, 1.8 grams of 6-hydroxy-5-nitro-2-(propylmercapto)-4(3H)-pyrimidinone, 15mL of phosphine oxychloride and 2mL of N,N-diethylaniline were refluxed Three hour preparation of 4,6-dichloro-5-nitro-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/38
CPCC07D239/38
Inventor 蒋成君韩小瑜王永江
Owner ZHEJIANG UNIVERSITY OF SCIENCE AND TECHNOLOGY
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