Novel preparation method for Istradefylline

Abstract

The invention relates to a preparation method for Istradefylline represented by a formula (I) shown in the description. The method comprises the following steps: subjecting 6-amino-1,3-diethyl-5-nitroso-1H-pyrimid-2,4-dione represented by a formula (II) shown in the description, which serves as a raw material, to catalytic reduction and salt forming, so as to obtain 5,6-diamino-1,3-diethyl-1H-pyrimid-2,4-dione hydrochloride represented by a formula (III) shown in the description; then, carrying out acetylation on the compound (III), so as to obtain N-(6-amino-1,3-diethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimid-5-yl)acetamide represented by a formula (IV) shown in the description; carrying out further ring closing, so as to obtain 1,3-diethyl-8-methyl-1H-purin-2,6(3H,7H)-dione represented by a formula (V) shown in the description; and carrying out methylation on the compound (V) firstly, and then, subjecting the methylation product to a condensation reaction with veratraldehyde represented by a formula (VII) shown in the description, thereby obtaining the end product Istradefylline. According to the novel preparation method for the Istradefylline, provided by the invention, raw materials, which are readily available industrially and are low in price, are used, the production process is more environmentally friendly, and the obtained product Istradefylline is high in yield and purity, thereby having a relatively high practical value.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a preparation method of istradefylline. Background technique [0002] Itradefylline is a new type of anti-Parkinson drug developed by Kyowa HakkoKirin Co., Ltd. in Japan. It was approved for marketing in Japan in 2013 under the trade name NOURIAST. Itradefylline is a selective adenosine A 2A Receptor (A 2A ) blocker, through the dual regulation of the striatal-pallidal pathway, reverses the imbalance of the direct and indirect pathways of the basal ganglia, improves the dyskinesia of Parkinson's disease, prolongs the action time of levodopa, but does not increase dyskinesia. Itradefylline has neuroprotective effects on substantia nigra dopaminergic neurons. It has been confirmed by clinical trials that istradefylline is a novel drug for effective treatment of Parkinson's disease. [0003] The chemical name of istradefylline is: ( E )-8-(3,4-dimethoxystyryl)-1,3-...

AI Technical Summary

Problems solved by technology

[0007] In this process, intermediate A (5,6-diamino-1,3-diethyl-1 H -pyrimidine-2,4-dione) is an unstable amine compound and is not easy to preserve; in the process of preparing intermediate B, the 3,4-dimethoxycinnamoyl chloride used needs to be prepared using thionyl chloride , the acid mist produced not only corrodes the equipment greatly, but also causes the ozone hole; and through the reaction of 3,4-dimethoxycinnamic acid, it is necessary to use a condensing agent that is expensive and has extremely poor atom economy1 -(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDAC), and nitrogen-containing waste water is produced in the post-treatment process; the solvent HMDS (hexamethyldi Silazane), the solvent is expensive, flammable and easily oxidized, and the reaction conditions are harsh, so it is not commonly used in production

[0008] Therefore, the existing common preparation process of istradefylline has defects such as high process difficulty, relatively high raw material cost, and poor atom economy, which cannot meet the needs of industrial production.

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