Method for preparing 2-chloropyrimidine

Abstract

The invention discloses a method for preparing 2-chloropyrimidine, belonging to the technical field of methods for preparing chemical medicine intermediates. The method for preparing the 2-chloropyrimidine comprises the following steps of: (1) reacting dicyandiamide with ammonium chloride at high temperature, and obtaining guanidine hydrochloride; (2) reacting the guanidine hydrochloride with 1.1.3.3-tetramethoxypropane by refluxing under the condition of taking industrial hydrochloric acid as a solvent to obtain 2-amino pyrimidine; and (3) reacting the 2-amino pyrimidine with sodium nitrate at low temperature for producing the 2-chloropyrimidine by taking zinc chloride as a catalyst and taking the industrial hydrochloric acid as the solvent. The preparation method disclosed by the invention has the advantages of lower cost of raw materials, relatively simple technical process, mild reaction conditions, low operation difficulty, excellent maneuverability; convenience for post-treatment; and largely improved yield stable quality and applicability of large-scale industrial production of prepared products,.

Description

technical field [0001] The invention belongs to the technical field of preparation methods of chemical drug intermediates, and in particular relates to a method for preparing 2-chloropyrimidine. Background technique [0002] 2-Chloropyrimidine is an important intermediate used in the synthesis of many new drugs. At present, domestic related literature reports the 10th issue of the 18th volume of "Chemical Industry Times" in October 2004, disclosing the synthesis report of 2-chloropyrimidine, which uses very rare and expensive raw materials diethyl malonate and dramatic diethyl malonate on the market. Poisonous and highly polluting phosphorus oxychloride, and zinc powder, which is very troublesome for post-processing, and the yield is very low, it is difficult to realize industrial production. [0003] In 2009, "Chemical Reagents", Volume 31, Issue 2, 149-150, disclosed the synthesis report of 2-chloropyrimidine, which used 1.1.3.3-tetramethoxypropane and guanidine hydrochlo...

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Problems solved by technology

At present, domestic related literature reports the 10th issue of the 18th volume of "Chemical Industry Times" in October 2004, disclosing the synthesis report of 2-chloropyrimidine, which uses very rare and expensive raw materials diethyl malonate and dramatic diethyl malonate on the market. Poisonous and highly polluting phosphorus oxychloride, and zinc powder, which is very troublesome to post-process, and the yield is very low, it is difficult to realize industrial production

[0003] In 2009, "Chemical Reagents", Volume 31, Issue 2, 149-150, disclosed the synthesis report of 2-chloropyrimidine, which used 1.1.3.3-tetramethoxypropane and guanidine hydrochloride, but the amount of guanidine hydrochloride was huge and expensive. At the same time, the subsequent treatment uses a large amount of hot toluene to extract, and it is difficult to meet the requirements of the three wastes in factory operation, and the cost is too expensive to realize industrial production.

[0004] In addition foreign relevant documents US2477409 (1946), JACS (1954), vol 76, p1065~1067, JACS (1951) vol 73, p5752~5756, disclosed the synthetic report of 2-chloropyrimidine, and the raw material that it uses is the The very rare and expensive raw material 2-aminopyrimidine is too expensive to realize industrial production; Tetrahedron letters 2000 vol 41, p1653-1656, the raw material used in the literature is reported to be the rare and expensive raw material 2- Hydroxypyrimidine is too expensive to realize industrial production; US4256888 (1981), JOC2006, vol 71, p1080-1084, the reported raw material also uses extremely expensive 2-mercaptopyrimidine, which is too expensive to realize industrialization cost advantage

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