Preparation method and application of suvorexant intermediate

Abstract

The invention provides a preparation method and application of a suvorexant intermediate, and relates to the technical field of chemical synthesis. The preparation method of the suvorexant intermediate comprises the following step: (e) reacting a compound as shown in a formula IV under the action of a Grubbs catalyst to obtain a compound as shown in a formula V. The Grubbs catalyst (Grubbs second-generation catalyst) is creatively used for construction of the suvorexant intermediate seven-membered nitrogen-containing chiral heterocycle, an inflammable and highly toxic compound methyl vinyl ketone is not needed, inflammable and explosive toxic gas is not needed, reaction is not needed under the conditions of strong acid, strong alkali and high temperature, generation of a large amount of acid liquor and alkali liquor and high-temperature operation can be avoided, the method is mild in reaction condition, environment-friendly, high in safety coefficient and easy to industrialize.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a preparation method and application of a Suvoryxan intermediate. Background technique [0002] Insomnia is the most common sleep disorder, about 30-50% of adults have shown symptoms of insomnia, of which 10-15% have been diagnosed with insomnia. Although insomnia is related to many serious physical and mental diseases, people's attention to him is far from enough. For a long time, insomnia is only defined as a symptom of other diseases, so there is little progress in understanding and treating it. . [0003] At present, the drugs for clinical treatment of insomnia mainly include benzodiazepine receptor agonists, melatonin receptor agonists and antidepressants with hypnotic effect, but the main purpose of most of them is not to treat insomnia, but to act as a sedative . Orexin is a neuropeptide produced by neurons in the hypothalamus, which plays an important role i...

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Problems solved by technology

At present, some documents, such as: US2008 / 132490, Org.Process Res.Dev.2011, 15:367-375, WO2012148553, J.Am.Chem.Soc.2011, 133:8362-8371, Org.Lett., 2012 , 14(13):3458-3461, Angew.Chem.Int.Ed.2011, 50, 11511-11515, J.Med.Chem., 2010, 14(53):5320-5332, Chin.Chem.Lett, 2015, 1(26): 103-107, Tetrahedron Lett, 2014, 42(55): 5778-5780, etc. During the preparation process, in order to obtain the intermediate seven-membered nitrogen-containing chiral heterocycle, chiral raw materials were used in some reactions Preparation, high cost; some reactions use highly toxic compound methyl vinyl ketone to construct; some reactions use a large amount of strong base and strong acid, resulting in excessive waste acid and waste alkali; some reactions have too high temperature , the reaction conditions are harsh, the risk factor is high, and it is not easy to realize industrialization

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