Method for preparing rasagiline mesylate

Abstract

The invention relates to a new preparation method for rasagiline mesylate for a Parkinson's disease resistant medicament, and belongs to the technical field of rasagiline mesylate preparation. The method comprises the following steps of: introducing a chiral auxiliary agent into 1-indenone (II) serving as a raw material, and performing reduction reaction to obtain a compound (III); then reacting the obtained compound (III) and 3-propiolic halide to obtain a compound (IV); and finally, dripping methylsulfonic acid into the obtained compound (IV) at a certain temperature in a certain solvent toobtain rasagiline mesylate (I). The method has the advantages of chiral synthesis, unique reaction route, good selectivity, high yield and a few reaction steps, and is simple and convenient to operate. The raw materials used for the reaction route are cheap and easily obtained, the cost is low, the optical purity is high, and the method is suitable for industrialized production. The method solvesthe problems of high cost due to the adoption of a key intermediate R-1-indamine, low reaction yield, long reaction steps and disadvantage on industrialized production in the conventional rasagiline mesylate synthesis process.

Description

Technical field: [0001] The invention relates to a new preparation method for anti-Parkinson's disease drug rasagiline mesylate, belonging to the technical field of rasagiline mesylate preparation. Background technique: [0002] Rasagiline mesylate (R)-N-2-Propynyl-1-indanamine methanesul-fonate is a drug for single or auxiliary levodopa treatment of Parkinson's disease. One of the main features of the pathological changes of Parkinson's disease is the degeneration of dopamine neurons, resulting in insufficient release of dopamine. As an irreversible selective monoamine oxidase-B (MAO-B) inhibitor, rasagiline mesylate can enhance the transduction signal of dopamine, block the decomposition of dopamine in the brain, and increase the extracellular level of dopamine in the striatum , elevated dopamine levels and subsequent increases in dopaminergic activity also have dopaminergic motor dysfunction. In addition, unlike other anti-Parkinson's disease drugs, the drug also has ne...

AI Technical Summary

Problems solved by technology

[0006] The shortcoming of this synthetic technique is: 1. the cost of the key intermediate R-1-indenamine is relatively high; 2. the reaction yield is low; 3. the reaction steps are too long, which is unfavorable for industrialized production

[0010] The shortcoming of this synthetic technique is: 1. except generating the desired secondary amine of propargyl monosubstituted on the nitrogen of 1-indenamine, simultaneously generates the tertiary amine of double replacement, has reduced reaction yield; 2. 1-indenamine is expensive, and The existence of side reactions leads to an increase in the production cost of this route; ③ there is a resolution process, and the yield is too low; ④ the product needs to be purified by column chromatography, distillation, etc., which also limits the use of this process for industrialized large-scale production

[0014] The disadvantage of this process is: 1-chloroindene or 1-bromoindene is unstable and prone to self-elimination reaction

[0017] The disadvantage of this process is: the side reaction of imine is serious, which is not conducive to industrial production

[0018] Although many synthetic schemes for synthesizing rasagiline have been reported in the prior art, there are certain defects as mentioned above, which are unfavorable for industrialized production

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