A kind of method for efficiently preparing aripiprazole intermediate

Abstract

The invention provides an efficient preparation method of an aripiprazole intermediate, and in particular relates to an efficient preparation method of aripiprazole intermediate BBQ (7-(4-bromobutoxy)-3,4-dihydro-quinolone), and the efficient preparation method of the aripiprazole intermediate comprises the use of a heteropoly acid or heteropoly acid salt and a phase transfer catalyst to form a composite catalyst and the use of a ketone (alcohol)-water azeotropic system. According to the method, in an etherification reaction, a low boiling point lower ketone and the heteropoly acid or the heteropoly acid salt and the phase transfer catalyst are used, the reaction temperature is reduced, at least 6 times molar equivalent of 1, 4-dibromobutane reacts with 7-hydroxy-3, 4-dihydro quinolone, and the formation of disubstituted substances can be reduced, a non-polar solvent is used for precipitation of the aripiprazole intermediate BBQ (7-(4-bromobutoxy)-3,4-dihydro-quinolone), and meanwhile the 1, 4-dibromobutane is recycled. The efficient preparation method of the aripiprazole intermediate has the advantages of high yield, high purity, simple procedure, low cost, and safe and reliable operation, and is friendly to the environment, low in energy consumption, and suitable for industrial mass production.

Description

Technical field: [0001] The present invention relates to a method for efficiently preparing an aripiprazole intermediate, in particular to an efficient preparation of an aripiprazole intermediate BBQ (7-(4-bromobutoxy)-3,4-dihydroquinolone) Method. The method for efficiently preparing an aripiprazole intermediate comprises using a heteropolyacid or a heteropolyacid salt and a phase transfer catalyst to form a composite catalyst and using a ketone (alcohol)-water azeotropic system. Background technique: [0002] Schizophrenia is the most common type of neurological disease caused by excessive neurotransmission activity of the dopaminergic nervous system in the central nervous system. Some active drugs that block the neurotransmission of dopaminergic receptors in the central nervous system have been developed. For example, Among the drugs developed are compounds of the phenothiazine type such as chlorpromazine; compounds of the butyrylbenzene type such as haloperidol; and comp...

AI Technical Summary

Problems solved by technology

In 2007, the US FDA approved it as an adjuvant drug for major depressive disorder. It showed a positive effect on dopamine D 2 and D 3 , 5-hydroxytryptamine 5-HT 1A and 5-HT 2A dopamine D 4 , 5-hydroxytryptamine 5-HT 2C and 5-HT 7 、a 1 - Epinephrine and Histamine H 1 receptors, and moderate affinity for serotonin reuptake sites. Moreover, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors. Aripiprazole The mechanism of action, like other drugs with efficacy in schizophrenia, remains unknown. However, it has been proposed that aripiprazole functions by 2 and 5-HT 1A Partial agonist activity of the receptor and the 5-HT 2A It is mediated by the combination of antagonist activity of receptors. Especially when the drug can reduce the undesired side effects, it is still highly desirable to be able to effectively improve the negative symptoms of schizophrenia and effectively improve the positive symptoms of schizophrenia. drug.

[0010] After our verification, the reported effect has not been achieved. Other units and individuals have also conducted some research on aripiprazole, but the overall effect is not stronger than them. Some even use more toxic reagents and excipients, which are not friendly to the environment. , some require special equipment and high temperature.

Images