PL179785B1 - Method of obtaining 1-(2-pyrimidinyl) piperazine - Google Patents

Abstract

1. Method for the production of 1- (2-pyrimidinyl) pipcra / .in, consisting in the condensation of piperazine with 2-chloropyrimidine in a solvent, characterized in that it is added to the piperazine 2-chloropyrimidine is used, preferably in portions.

Description

The subject of the invention is a method for the preparation of 1- (2-pyrimidinyl) piperazine, which is used as an intermediate for the synthesis of many pharmacologically active substances, including in particular the valuable alcoholic drug buspirone and the dopaminergic drug pyribedil.

The method of preparation of 1- (2-pyrimidinyl) piperazine is known from the prior art, described in the article by K.L. Howard et al. in J. Org. Chem., 18 (1953), page 1487, which involves the condensation of piperazine with 2-chloropyrimidine. In a known process, a solution of both reagents in 95% ethanol is heated to reflux. The efficiency of the process carried out in this way is about 60% (based on 2-chloropyrimidine).

The aim of the invention is to increase the yield of the reaction for the preparation of 1- (2-pyrimidinyl) piperazine, and thus to reduce the consumption of expensive starting materials, especially 2-chloropyrimidine, and to improve the purity of the product.

It turned out that the efficiency of the reaction depends on the sequence of dosing the reactants into the reaction vessel.

The process according to the invention consists in that the condensation reaction of piperazine with 2-chloropyrimidine is carried out by adding 2-chloropyrimidine to the piperazine, preferably in portions.

With this type of reaction, the amount of the main by-product (piperazine disubstitution product) is minimized as piperazine is in excess of 2-chloropyrimidine at any time in the reaction.

The reaction can be carried out in an inert organic solvent that dissolves both reactants, for example methanol, ethanol or water, or in an organic solvent-water mixture.

In a preferred embodiment of the process according to the invention, the reaction is carried out in an aqueous solution.

The reaction can be carried out at a temperature between room temperature and reflux temperature. Preferably the reaction is carried out at the reflux temperature of the reaction mixture.

The process according to the invention provides a reaction yield of about 30% higher than in the conventional method, based on 2-chloropyrimidine.

When the reaction is carried out in aqueous solution, the additional advantageous effect is that the isolation of the reaction product is easier and the purity of the product is increased due to the difference in solubility of the substrate and the product in water.

Example. Piperazine (30 g, 0.35 mol) was suspended in 110 cm ^{3 of} water, the mixture was heated to reflux and a solution of 2-chloropyrimidine in 140 cm 3 of water was added in portions over 45 minutes. The mixture was then heated for an additional 20 minutes and left at 4 ° C for 12 hours. The resulting white precipitate was filtered off, and the filtrate was extracted with five 100 ml portions of chloroform. The combined chloroform extracts were dried over anhydrous potassium carbonate, the drying agent was removed by filtration, and the solvent was distilled off under reduced pressure of 2.66 kPa (20 mm of Hg) to give 19.7 g of product (91% yield based on 2-chloropyrimidine).

Publishing Department of the UP RP. Circulation of 60 copies

Price PLN 2.00.

Claims (3)

Patent claims A method for the preparation of 1- (2-pyrimidinyl) piperazine, which consists in condensing piperazine with 2-chloropyrimidine in a solvent, characterized in that 2-chloropyrimidine is added to the piperazine, preferably in portions. 2. The method according to p. The process of claim 1, wherein the reaction is carried out in an aqueous solution. 3. The method according to p. The process of claim 1 or 2, wherein the reaction is carried out at the boiling point of the reaction mixture.