KR790001667B1 - Process for the preparation of bis-trimethoxy benzyl piperazyno alkanes - Google Patents

Abstract

Title compds. (I; n = 2-8), having coronary-vasodilating action, cardiac activity-lowering ! action and useful for treating ischemic heart disease, were prepd. by reacting 2 mol tri- methadizine(II) and 1mol dihalogenoalkane, benzylating dipiperazinoalkane, or decyclizing piperazine ring with 2mol activated derivatives of N-benmediethanol-amine and 1mol diaminoalkane.

Description

Preparation of bis trimethoxy benzyl piperazino alkanes

This invention relates to the manufacturing method of bis trimethoxy benzyl piperazino alkanes represented by the following general formula (I).

Where n is an integer from 2-8

The compound of the present invention has a pharmacological action such as coronary vasodilatation, cardiovascular activity, and the like as a novel substance in the literature, and is useful as a therapeutic agent for ischemic heart disease.

As an example of these pharmacological actions, Table 1 shows the activity of cardiovascular vessels by the Langndroff method and LD ₅₀ values of mice in the molar extract heart.

[Table 1]

Any of these compounds can be synthesized by various methods, but the most common one can be easily synthesized by acting 1 mole of dihalogenoalkanes on 2 moles of trimethadizine represented by the following chemical formula (II). In addition, a method of benzylating dipiperazino alkanes or a method of ring closing the piperazine ring by 2 moles of an activated derivative of N-benme diethanol amine and 1 mole of diamino alkanes is also advantageously used.

It will be described in more detail by the following examples.

Example 1 (n = 2)

10.0 g of hydrochloride (I hydrochloride, 13 g of anhydrous potassium carbonate and 5.6 g of dibroethane) were heated and stirred at 50-60 ° C. for 3 hours in 100 ml of DMF, and the basic material obtained by treatment according to the following method was recrystallized with acetone.

Example 2 (n = 4)

5.0 g of hydrochloride of compound (II), 9.0 g of anhydrous potassium carbonate, and dichlorobutane 1.0 were heated and stirred at 60-70 ° C. for 10 hours in 100 ml of DMSO, and treated according to the following method. The basic substance was extracted with chloroform and the chloroform extract was extracted. The mixture was shaken with dilute acid, the hydrochloric acid layer was made alkaline and the target substance was extracted with ether. 4 mol of maleic acid is added and it recrystallized with isopropanol as maleic acid salt.

Melting Point 95-98 ° C., Yield 1.50 g

Example 3 (n = 6)

6.7 g of Compound (II) hydrochloride, 1.8 g of dichlorohexane, and 7.0 g of anhydrous potassium carbonate were heated and stirred at 50-60 ° C. for 6 hours in 70 ml of DMF, and treated according to a conventional method. Back extract with water and obtain the target product in the acetic acid layer. Recrystallized from hydrous dioxane with hydrochloride. Melting point 230 ° C. (decomposition), yield 0.95 g.

Example 4 (n = 8)

9.0 g of the compound (II) hydrochloride, 3.0 g of dichlorooctane and 16 g of anhydrous potassium carbonate were warmed and stirred at 65-70 ° C. for 12 hours in 70 ml of DMF, and treated in the same manner as in Example 3 below, and recrystallized with hydrous isopropanol as hydrochloride. . Melting point 230 ° C or higher (decomposition), yield 2.2g

Claims (1)

A method for preparing bistrimethoxy sibenzyl piperazino alkanes of the following general formula (I), which is characterized by acting 1 mole of dihalogenoalkanes to 2 moles of trimethadizine of the general formula (II).

(Where n is an integer from 2-8)