CS209752B1 - Method of preparing alkyl-1-methyl-1,2,3,4-tetrahydro-9h-pyrido/3,4-b/indol-1-carboxylates - Google Patents

Abstract

The present invention relates to a process for the preparation of alkyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido (3) 4-b) indole-1-carboxylates of formula I H3C wherein R is C 2 -C 4 alkyl by reacting tryptamine hydrochloride with the pyruvic acid ester of formula III H 3 C - CO. COOR ’(III) wherein R is the same as in Formula I, in an alkanol of 1 to 3 carbon atoms, at the boiling point of the reaction mixture. The new substances obtained are intermediates of drug synthesis.

Description

(54) A process for the preparation of alkyl-1-methyl-N, N-tetrahydro-SH-pyrido O, N-indole-1-carboxylates

The present invention relates to a process for the preparation of alkyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido [3,4-b] indole-1-carboxylates of the formula I

H ₃ C wherein R is C 2 -C 4 alkyl, by reaction of tryptamine hydrochloride with a pyruvic acid ester of formula III

H ₃ C-CO. COOR '(III), wherein R is the same as in Formula I, in a C 1 -C 3 alkanol medium, at the boiling point of the reaction mixture. The new substances obtained are intermediates in drug synthesis.

The present invention relates to a process for the preparation of alkyl 1-methyl-1,2,3,4-tetrahydro-9H-pyrido [3,4-b] indole-1-carboxylates of the formula I

V \ A / ^{NH (I) &} gt ;.

^H / COOR h ₃ c in which R represents alkyl of 2 to 4 carbon atoms. These compounds are all novel and are valuable intermediates in the synthesis of heterocyclic drugs.

According to the invention, they are prepared by tryptamine hydrochloride of formula II

⁽ Ii ⁾ NH 3 · HCl

H is heated to boiling with a stoichiometric amount, preferably with an excess of 0.02 to 0.05 mol, of the pyruvic acid ester of formula III

H3C. CO. COOR (III) in which R is the same as above in a polar organic solvent, for example a C 1 -C 3 alkanol, preferably methanol or ethanol.

In the process according to the invention, a mixture of tryptamine hydrochloride with a small excess of the pyruvic acid ester of the formula III, most often in ethanol or methanol, is boiled for 20-25 h and then processed to the final product which is purified by crystallization and / or chromatography.

Instead of a polar organic solvent, for example said C 1 -C 3 alkanols, aprotic solvents such as dimethylformamide may also be used.

Tryptamine hydrochloride of formula I may be replaced by another mineral acid salt in the reaction, or tryptamine alone may be used; however, this alternative is disadvantageous in that it is necessary to prepare the aforementioned salts, respectively. free tryptamine.

The following Examples illustrate but do not limit the generality of the process of the invention.

Example 1

To a solution of 101.9 g (0.518 mol) of tryptamine hydrochloride (compound of formula II) in 1600 ml of ethanol is added 66.17 g (0.57 mol) of ethylpyruvate (compound of formula III, R is ethyl), and the mixture is heated to boiling. 20 h evaporate to dryness in vacuo. The residue is dissolved in 1 liter of warm water and extracted twice with 200 ml of benzene each. The aqueous solution was basified with concentrated aqueous ammonia solution to pH 10-12 and the precipitated product was taken up in methylene chloride (3 x 250 ml). The combined organic phases are washed with 100 ml of water and, after drying, evaporated on a rotary evaporator. The residue was recrystallized from a mixture of chloroform, benzene and petroleum ether. The precipitated crystals are aspirated and dried. 110.4 g (82.5% of theory) of ethyl 1-methyl-1,2,3,4-tetrshydro-9H-pyrido (3,4-b) indole-1-carboxylate (compound of formula I, R) are obtained. 114 DEG-115 DEG.

Example 2

A mixture of 19.67 g (0.1 mol) of tryptamine hydrochloride (compound of formula II), 17.3 g (0.12 mol) of butylpyruvate (compound of formula III, R is butyl) in 200 ml of anhydrous methanol is heated to boiling for 25 h. After cooling, the reaction mixture was basified with concentrated aqueous ammonia solution and evaporated on a rotary evaporator. The residue is partitioned between 150 ml of water and 250 ml of methylene chloride. The organic phase is concentrated to a volume of about 40 to 50 ml and loaded onto a 60 g silica gel column. The column was washed with a 1: 1 mixture of benzene and chloroform and the eluate was evaporated in vacuo. The residue was crystallized from a mixture of benzene, acetone and petroleum ether to give 18.64 g (65.1% of theory) of butyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido (3,4-b) indole-1. -carboxylate (compound of formula I, R is butyl), m.p. 71-73 ° C.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of alkyl 1-methyl-1,2,3,4-tetrahydro-9H-pyrido (3,4-b) indole-1-carboxylates of formula I (I) wherein R is alkyl of 2 to 4 atoms The composition of claim ₁ wherein the tryptamine hydrochloride of formula II is nh ₂ H is heated to boiling with a stoichiometric amount, preferably with an excess of 0.02 to 0.05 mol, of the pyruvic acid ester of formula III H ₃ C. CO. COOR (III), wherein R is the same as above, in a polar organic solvent, for example a C 1 -C 3 alkanol, preferably methanol or ethanol.