CS261296B1 - Process for the preparation of new 2- (ethoxycarbonyl) -2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indoles - Google Patents

Abstract

The solution falls into the field of synthesis of pharmacodynamically active substances usable as drugs. Its subject is a method for preparing new 2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-pyrido/3,4-b/indoles consisting in the reaction of the respective 2-unsubstituted substances with ethyl chloroformate in boiling benzene. The solution describes the preparation of 2-(ethoxycarbonyl)-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido/3,4-b/indole, 2-(ethoxycarbonyl)-1- (2-(2-dimethylaminoethoxy)phenyl-2,3,4,9- -tetrahydro-1H-pyrido/3,4-b/indole and its hydrochloride.

Description

The present invention relates to a process for the preparation of the novel 2- (ethoxycarbonyl, -2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indoles of formula I).

wherein R is hydrogen or 2-dimethylaminoethoxy.

The compounds of the formula I are intermediates in the synthesis of pharmacodynamically active substances and as such are technically important.

The process for the preparation of the compounds of the formula I according to the invention consists in reacting the compounds of the formula II

wherein R is the same as in Formula I, with ethyl chloroformate. The reaction can be carried out in any inert atmosphere at elevated temperature, and it has proven particularly useful to work in benzene at the boiling point of the solvent. Of the starting materials, 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (II, R = H) is a known substance (Skinner W. A., Parkhurst R. M., Can.

J. Chem. 43, 2251 (1965). 1- (2- (2-dimethylaminoethoxy) phenyl) -2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (II, R = OCH3CH3NfCH3) ₂ ) is a new substance and its preparation is described in the example. The examples provide further details of the process for the preparation of the compounds of formula (I) according to the invention, which are merely illustrative of the possibilities of the invention and are not intended to exhaustively describe all possibilities of the invention.

Example 1

2- (ethoxycarbonyl) -1-phenyl-2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (I, R-H)

Warm solution (60 ° C) 6.2 g of 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (literature cited) in 100 ml of benzene was added dropwise to the stirred solution 3. 25 g of ethyl chloroformate in 40 ml of refluxing benzene. The mixture was refluxed for 2 h and then cooled. The precipitated hydrochloride of the starting material (II, R = H) (3.3 g, mp 264-268 ° C) is suction filtered, the filtrate is washed with 10% sulfuric acid and water, dried over magnesium sulphate and evaporated. 3.8 g (47%) of the title compound are obtained, which crystallizes from benzene and melts in the pure state at 192-193 ° C.

Example 2

2- (ethoxycarbonyl) -1- (2- (2-dimethylaminoethoxy) phenyl-2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (I, R = OCH ₂ CH ₂ N ( CH ₃ ) ₂

A solution of 5.0 g of 1- (2- (2-dimethylaminoethoxy) phenyl) -2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole in 60 ml of benzene was added dropwise to stirred and refluxed. with a boiling solution of 1.95 g of ethyl chloroformate in 40 ml of benzene and boiling the mixture for 4 h. After cooling, 5.5 g (91%) of the hydrochloride of the desired product are isolated by filtration. Mp 231-234 ° C. Crystallization from aqueous ethanol / ether yields the monohydrate, melting at 155-160 ° C.

Starting 1- (2- (2-dimethylaminoethoxy) phenyl) -2,3,4,9-tetrahydro-1H-pyrido [3,4-b] indole (II, R = OCH ₂ CH ₂ N (CH ₃ ) i) ), which has not yet been described in the literature, is obtained, for example, by the following procedure using the synthesis of Pictet and Spengler (whaley WM, Govindachari TR:

Org. React. 6, 151 (1951).

A mixture of 9.65 g of 2- (2-dimethylaminoethoxy) benzaldehyde (U.S. Pat. No. 2,879,293), 9.80 g of tryptamine hydrochloride (Adlerová E. et al .: Collect. Czech. Chem. Commun. 25, 784, 1960) )

125 ml of ethanol, 50 ml of benzene, 2.5 ml of water and 5 drops of hydrochloric acid are stirred and refluxed for 12 h. After standing overnight at room temperature, the hydrochloride of the desired compound is isolated by filtration and the mother liquor is worked up in the usual manner. A total of 17.0 g (92%) of this hydrochloride is obtained, which is pure after crystallization from ethanol and melts at 254-258 ° C. Decomposition of this hydrochloride (15.0 g) with 300 ml of 10% sodium hydroxide solution liberates the base which is isolated by extraction with ether. Working up of the extract yielded 10.2 g of base which crystallized from benzene and melted at 130-131 ° C.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of the novel 2- (ethoxycarbonyl) -2,3,4,9-tetrahydro-1H-pyrido [2,3-b] indoles of formula I wherein R is hydrogen or 2-dimethylaminoethoxy, characterized in that: the compounds of formula II NH (II), in which R is the same as in Formula I, is reacted with ethyl chloroformate in boiling benzene.