Tiagabine ethyl ester hydrochloride and preparation method thereof

Abstract

The invention provides a tiagabine ethyl ester hydrochloride as shown in a formula 3. The invention also provides a preparation method of the compound as shown in the formula 3. The tiagabine ethyl ester hydrochloride provided by the invention can be used as an impurity reference substance for tiagabine hydrochloride, and more convenient for control over the impurity content in the product production process and the finished product quality detection process. According to the preparation method provided by the invention, the tiagabine ethyl ester hydrochloride having the purity of more than 99.9% is finally prepared from specific reaction raw materials in combination with a corresponding refining process, and the product can be directly used as the reference substance to control the content of related substances of tiagabine hydrochloride.

Description

technical field

[0001] The invention relates to tiagabine ethyl ester hydrochloride and a preparation method thereof. Background technique

[0002] Tiagabine hydrochloride (Tiagabine hydrochloride, 1) is the first marketed neuron and glial γ-aminobutyric acid (GABA) reuptake selective and reversible inhibitor, which can inhibit mediator transmission in the central nervous system, It increases the concentration of GABA in the synapse and reduces the sensitivity of nerve excitation. It is an antiepileptic drug with a very clear mechanism of action. The chemical name of tiagabine hydrochloride is (R)-(-)-N-[4,4-bis-(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid Hydrochloride, the structural formula is as follows:

[0003]

[0004] The synthetic route of the now reported tiagabine hydrochloride mainly takes 2-bromo-3-methylthiophene as starting material, synthesizes N-alkylating reagent by different methods, and then reacts with chiral ethyl piperidinecarboxyla...

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