Process for synthesis of 3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile, and application in synthesis of ivabradine
By using a base to react with the compound of formula (VIII) in an organic solvent and combining reduction and bromination reactions, the synthesis yield of 3-(2-bromo-4,5-dimethoxyphenyl)propionitrile was successfully improved. It solves the problem in the existing technology that intermediates in the synthesis of ivabradine are difficult to obtain efficiently, and provides a more effective drug production path for treating myocardial ischemia and arrhythmia.
Patent Information
- Application Number
- CN201310651955.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2012-12-06
- Filing Date
- 2013-12-05
- Publication Date
- 2014-06-11
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
It is difficult to synthesize 3-(2-bromo-4,5-dimethoxyphenyl)propionitrile with high yield using existing technology, which is the key intermediate for the synthesis of ivabradine and its addition salt with pharmaceutically acceptable acids. body, affecting its industrial application in the treatment of myocardial ischemia and arrhythmia.
The compound of formula (I) is obtained by reacting the compound of formula (VIII) with a base in the presence of propionitrile in an organic solvent, preferably using n-butyllithium as the base, and controlling the reaction temperature at -65°C to 25°C. The method includes converting the compound of formula (IX) into the compound of formula (VIII) through reduction and bromination reactions, and performing an intramolecular cyclization reaction in an alkaline medium to finally obtain ivabradine.
The synthesis yield of 3-(2-bromo-4,5-dimethoxyphenyl)propionitrile is improved, a more efficient method is provided to produce ivabradine and its hydrochloride, and its use in Pharmacological properties in the treatment of myocardial ischemia and arrhythmias.