DD285982A5 - METHOD FOR THE PRODUCTION OF SUBSTITUTED THIAZOLO [4,5-B] -PYRIDINES - Google Patents

Abstract

The invention relates to a process for the preparation of substituted * The object of the invention is to develop a process for the preparation of 2-alkylthio (or * The substituted * are valuable intermediates for the preparation of pharmaceuticals or pesticides substituted N-nitroguanyl-dithiocarbimic acid monoesters with halogenated alkylidene malonitriles in polar solvents and in the presence of bases. {N-nitroguanyl-dithiocarbimide-acid monoesters; alkylidenemononitriles; 3-bromomethyl-2-cyanocinnamic acid nitriles; nucleophilic substitution; intramolecular cyclization; * carbonitriles }

Description

For this 1 page formulas

Application blot of the invention

The invention relates to a process for the preparation of substituted thiazolo [4,5-bjpyridines.

The thiazolo [4,5-b] pyridines according to the invention are valuable intermediates for the preparation of pharmaceuticals or agrochemicals.

Characteristic of the known state of the art

The class of substituted thiazolo [4,5-b] pyridines has not previously been described in the technical and patent literature.

Object of the invention

The aim of the invention is to develop a process for the preparation of substituted thiazolo [4,5-b] pyridines, which are of great value as intermediates for the preparation of pharmaceuticals or pesticides.

Explanation of the essence of the invention

The object of the invention is to enable a synthesis of novel substituted thiazolo [4,5-b] pyridines on the basis of monoesters of N-nitroguanyl-dithiocarbimic acid.

According to the invention, the substituted thiazolo [4,5-b-pyridines of the formula 3 in which R ^{1 is} substituted or unsubstituted alkyl or aralkyl groups and R ² corresponds to a substituted or unsubstituted aryl radical, by conversion of N-Nitroguar> yl-dithiocarbimidsäuremonoestern of formula 1, in which R ^{1 is the} same meaning as l.at, with halogenating Alkylidenm.'ilonitrilen of the formula 2, in which R ^{2 has the} above meaning and X corresponds to any halogen, in the presence of bases, preferably potassium hydroxide or triethylamine produced , - ».

SR ¹

C B

XH ₂ O ON

KOH. TEA

- KX

- N ₉ O

/ .. 'at 20 ° C to 70 ⁰ C. The reactions to give the pyridines substituted thiazolo [4,5-b] carried out in aqueous Dr. The

Final products are obtained by pouring the reaction solution into water in good yield. A cleaning is through Umkristallieation possible from ethanol or DMF / ethanol. The substituted thia2olo [4,5-b] pyridines are valuable intermediates for the preparation of pharmaceuticals or Pesticides. Auiführungtbeliplele

1. 5-Amino-2-methylthio-7-phenyl, 3Hiazolo [4,5-b] pyridine-6-carbonitrile.

0.01 mpl of N-nitroguanyl-dithiocarbimide-sour-monomethyl ester are dissolved in 40 ml of DMF and mixed with the equimolar amount

Potassium hydroxide in 5 ml of water. To the cooled to about 18 ⁰ C solution is added in portions 0.01 mol of 3-bromomethyl

2-cyari-zimtsfiurenitril. After the exothermic reaction, 1 ml of triethylamine to the reaction mixture and keeps it under constant stirring for about one hour at 60 ⁰ C. The cooled reaction solution is filtered off with suction in a large excess water poured, and the separating crystals are. The purification is carried out by recrystallization from DMF / ethanol.

Mp .: 226 ⁰ C. Yield: 2.5 g (83.9% of theory.).

Second 5-amino-2-ethylthio-7-phenyl-1,3-thiazolo [4,5-b) pyridine-6-carbonitrile

Analogously to Example 1, from 0.01 mol of N-nitroguanyl-dithiocarbamic acid monoethyl ester and 0.01 mol of 3-bromomethyl-2-cyano

cinnamic acid

Mp .: 202 ⁰ C. Yield: 3.0 g (96.4% of theory.).

3. 5-Amino-7-p-chloro-2-methylthio-1,3-thiazolo [4,5-b-pyridine-6-carbonitrile

Analogously to Example 1 from 0.01 mol of N-nitroguanyl-dithiocarbamic acid monomethyl ester and 0.01 mol of 3-8rommethyl-2-cyan-p

chloro-zimteäurenitril

M.p .: 179-181 ⁰ C. Yield: 2.9 g (87.0% of theory.).

O ₂ NN = C.

NH ₂

N = c

SH

R ² . .CN

> C:

X-CH ₂

H ₂ N NC

-SR ¹

WP

Claims (2)

A process for the preparation of substituted thiazolo [4,5-b] -pyridines of the formula 3 in which R ^{1 is} substituted or unsubstituted alkyl or aralkydyne groups and R ² corresponds to a substituted or unsubstituted aryl radical, characterized in that N-Nitroguanyldithiocarbimidsäuremonoester of formula 1, in which R ¹ has meaning above, with halogenated Alkylidenmalonitrilen of the formula 2, in which R ^{2 has the} above meaning and X corresponds to any halogen, in the presence of bases, preferably alkali metal hydroxides and tertiary amines, implemented. 2. The method according to claim 1, characterized in that the reactions in polar solvents, preferably dimethylformamide, in the presence of small amounts of water at 2O ⁰ C to 70 ⁰ C are performed.