4, 6-dichloro-2-methyl-5-(1-acetyl-2-imidazoline-2-yl)-aminopyrimidine preparation method

Abstract

The invention discloses a 4, 6-dichloro-2-methyl-5-(1-acetyl-2-imidazoline-2-yl)-aminopyrimidine preparation method. The preparation method includes: firstly, feeding concentrated nitric acid and concentrated sulfuric acid into diethyl malonate for nitrifying diethyl malonate to obtain diethyl 2-nitromalonate; secondly, enabling the diethyl 2-nitromalonate and acetamidine hydrochloride to cyclize to obtain 2-methyl-5-nitro-4, 6-dihydroxypyrimidine under the action of 12N hydrochloric acid; thirdly, chloridizing the 2-methyl-5-nitro-4, 6-dihydroxypyrimidine with sulfoxide chloride serving as a chlorinating agent and hydrogenating and reducing the chloridized 2-methyl-5-nitro-4, 6-dihydroxypyrimidine with Raney nickel; and finally, condensing a product obtained in the third step and acetyl imidazo-2-one, so that 4, 6-dichloro-2-methyl-5-(1-acetyl-2-imidazoline-2-yl)-aminopyrimidine is obtained. The preparation method is short in reaction time, higher than 80% in yield and simple and convenient to operate as reaction processes are carried out under the normal pressure, the 4, 6-dichloro-2-methyl-5-(1-acetyl-2-imidazoline-2-yl)-aminopyrimidine is low in production cost, phosphorus wastewater is avoided, and emission of waste gases, wastewater and industrial residues is low.

Description

technical field [0001] The present invention relates to the field of compounds having a pyrimidine structure and an imidazole structure, in particular to 4,6-dichloro-2-methyl-5-(1-acetyl-2-imidazolin-2-yl)aminopyrimidine compounds Preparation. Background technique [0002] Moxonidine is a widely used antihypertensive drug. In recent years, the demand for Moxonidine intermediates in the international market has been increasing, increasing at a rate of 20% per year. [0003] The traditional method uses acetamidine hydrochloride as a raw material, through cyclization, nitration, chlorination, reduction, addition dehydration, and alcoholysis to form a salt, and the product is synthesized with a total yield of 24.8%. In the chlorination reaction, phosphorus oxychloride was used as the chlorination agent, and the yield was 92.8%. In the reduction reaction, iron powder is used as the reducing agent, and steam distillation is carried out after the reaction is completed. This me...

AI Technical Summary

Problems solved by technology

This method has inherent defects: (1) Nitrification after cyclization first, resulting in a decrease in yield; (2) Phosphorus oxychloride is used as the chlorination agent in the chlorination process, and the amount of feed is too large, and the energy consumption of distillation and recovery of phosphorus oxychloride is large , the workshop hygiene requirements are high; (3) The reduction process uses "iron powder" as the reducing agent, which is a process that has been eliminated. The waste water of iron sludge is large and the pollution is serious.

[0004] Environmental pressure is high

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