PL168611B1 - Polycyclic imides - Google Patents

Abstract

1. Method of obtaining polycyclic imides of the general formula, where X butylamine, characterized in that the n (7-isopropyl-6-methyl-bicyclo) (2,2,2) octa-5-ene -2,3-dicarboximide is treated with 1-bromo-4-chlorobutane, to give a compound of the general formula where X is chlorobutyl then chlorobutylimide reacts with an amine, especially N-aryl piperazine giving a compound of the general formula, where X is butylamine

Description

The subject of the invention is a process for the preparation of polycyclic imides.

The compounds of the invention are new and not described in the literature. The new compounds have an affinity for the serotonin -5 HT _1A receptor, comparable to the new generation anxiolytic drug Buspirone. There are known methods for the preparation of N- (4-aryl -1-piperaz.ynylbutyl) imides of other bicyclic systems.

Many of the resulting bicyclic imide derivatives contain an N-pyrimidinyl-piperazinyl butyl moiety and exhibit selective anxiolytic activity. All these compounds are used in medicine.

According to the invention, the process for the preparation of polycyclic imides is that 7-iso-propyl-6-methyl-bicyclic (2,2,2) octa-5-ene-2,3-dicarboximide is treated with 1-bromo-4-chlorobutane to give chlorobutylimide. This compound reacts with an amine, especially N-α-rilopiperazine, to give a compound of the general formula where X is butylamine. The amine used is N - (- 2-pyrimidinyl) piperazine, 1- (- 2-pyridyl) piperazine, 1- (-2-methoxyphenyl) piperazine, 1- (- 4-fluorophenyl) piperazine. The resulting chlorobutylimide is purified by crystallization. Then it is performed in a compound of the general formula where X is butylamine by reaction with an amine, especially N - 4-aryl / -1-piperazine. The compound obtained is converted into the hydrochloride salt and purified by crystallization.

The method of preparation of the new compounds according to the invention is presented in more detail in the embodiment.

Example: 2.33 g (0.01 mol) 7-isopropyl-6-methyl-bicyclo / 2.2.2) octa-5-ene-2,3-dicarboximide, 30 cm ³ acetone, 1.72 g / 0, 01 mol (1-bromo-4-chlorobutane, 1.4 g (0.01 mol) of potassium carbonate, 0.25 g (0.0015 mol) of potassium iodide was heated for 30 hours under reflux. Then it was filtered and the excess of unreacted 1-bromo-4-chlorobutane and solvent was distilled off under reduced pressure.

The dry residue is extracted several times with small amounts of n-hexane. After crystallization from n-hexane, N- (4-chlorobutyl) -7-isopropyl-6-methyl-bicyclo (2.2.2) octa-5-ene-2,3-dicarboximide is obtained in the form of colorless diamonds, m.p. 49- 50 ° C / Ed. 89.6% /. A mixture of 3.25 g (0.01 mol) N- (4-chlorobutyl) -7-isopropyl-6-methyl-bicyclo (2.2.2) octa-5-ene-2,3-dicarboximide, 40 orf acetonitrile, 1.89 g (0.007 mol) of 1 - / - pyrimidinyl) piperazine dihydrochloride. 4.2 g (0.03 mol) of anhydrous potassium carbonate 0.25 g (0.0015 mol) of potassium iodide was heated to reflux for 30 hours. It is filtered, excess solvent is distilled off under reduced pressure, the dry residue is extracted several times with n-hexane and distilled off again. The dry residue is dissolved in 10 cm 3 of methanol and a few drops of methanolic hydrogen chloride solution are added.

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The product obtained: N - // 4- (4-pyr (midynyl) -piperazin-1-yl) -butyl) -7-iso-propyl-6-methyl-bicyclo (2.2.2) octa -5-eno -2,3-d (carboxy) dihydrochloride.

Colorless crystals are crystallized from methanol with the addition of diethyl ether, melting point: 195 - 190 ° C

Efficiency - 08.9%

C ₂₆ H ₃₉ O ₂ N ₅ C1 ₂ / 524.536 /

Computational analysis 59.53% C 0.50% H 13.33% N

Analysis found 59.95% C 0.51% H 13.26% N

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Publishing Department of the UP RP. Circulation of 90 copies Price PLN 1.50

Claims (2)

Patent claims A method for the preparation of polycyclic imides of the general formula wherein X is butylamine, characterized in that (7-isopropyl-6-methyl-bicyclo (2,2,2) octa-5-ene-2,3-dicarboximide is treated with 1 -bromo-4-chlorobutane to give a compound of the general formula where X is chlorobutyl, then the chlorobutylimide reacts with an amine, especially N-aryl piperase, to give a compound of the general formula where X is butylamine. 2. The method according to p. A process according to claim 1, characterized in that the amine used is N-aryl piperazine, such as: N - (- 2-pyrimidinyl) piperazine, 1- (2-pyridyl) piperazine, 1-2-pyridyl / piperazine, 1- (2-methoxyphenyl) piperazine , 1- (4-fluorophenyl) piperazine.