32 results about "Suvorexant" patented technology

The invention provides a synthesis method of a suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester. The synthesis method of the suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester comprises the following steps: (1) enabling a compound Suvor-1 to react with vitride solution to obtain a compound Suvor-2; enabling the compound Suvor-2 to react with 4,4-dimethoxy-2-butanone to obtain Suvor-3; (3) enabling the compound Suvor-3 to react with methanesulfonic acid to obtain a compound Suvor-4; (4) enabling the compound Suvor-4 to react with di-tert-butyl dicarbonate to obtain a compound Suvor-5; (5) enabling the compound Suvor-5 to react with hydrogen to obtain the suvorexant intermediate. The synthesis method of the suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester provided by the invention has the advantages that the reaction is simple, starting materials are cheap and easy to obtain, the reaction condition is mild, and the production safety is high; in addition, the reaction steps are less, the reaction yield is high, and the production cost is lower; moreover, by introducing a chiral functional group, the purity of a target product obtained after induced synthesis and ring closure is high, the amount of impurities in enantiomer is small, the ee% is greater than97%, and the method is suitable for commercial large-scale production.

The invention relates to a synthetic method for an intermediate of suvorexant as an anti-insomnia medicament. The synthetic method is characterized in that 4-methyl-2-hydrazinobenzoic acid hydrochloride is taken as a starting raw material, and reacts with glyoxal to generate dihydrazone; then dihydrazone is subjected to cyclization under the action of copper trifluoromethanesulfonate to obtain a key intermediate 5-methyl-2-(2H-1,2,3-triazole-2-yl) benzoic acid of the suvorexant as the anti-insomnia medicament. The synthetic method disclosed by the invention has the advantages of low price of raw materials, short reaction step, simpleness and convenience in operation, no isomers difficult to separate, high content of products and easiness for industrial production; meanwhile, a ring-closing by-product 4-methyl-2-carboxy anilide is separated in a form of forming hydrochloride, and is a raw materials for synthesizing the starting raw material 4-methyl-2-hydrazinobenzoic acid, so that organic materials can be recycled, and further the total synthetic cost is lower; in addition, by recovering treatment, solvent can be used indiscriminately, economy, environment friendliness and important application value are realized.

The present invention relates to a process for the preparation of a compound of formula (A), Further, the present invention relates to the respective compound (A) as such and to its use in the preparation of antifungal agent.

The invention belongs to the technical field of medicines and relates to a method for preparing an important intermediate {2-[(5-chlorobenzoxazole-2-yl)-(3-one-butyl)-amino]ethyl}-tert-butyl carbamate. A highly toxic product methyl vinyl ketone is substituted by a compound with low toxicity, and due to catalytic reactions of DBU, LDA, NaHMDS, KHMDS and the like, a compound of a formula (3) can be obtained at high yield of 90% or higher. Moreover, the HPLC (high performance liquid chromatography) content of the crude product reaches 99.5% or higher, and the method disclosed by the invention is suitable for industrial production.

The invention discloses a method for preparing a Suvorexantintermediate as shown in a formula 8A and an analogue thereof, or pharmaceutically acceptable salts and solvates thereof, wherein R is hydrogen or an alkyl group of C1 to C6. The method comprises the following steps of removing an amino protection group of a compound as shown in a formula 3 to obtain a compound as shown in a formula 4A; d, adopting the compound as shown in the formula 4A for preparing to obtain a compound as shown in a formula 5A; e, adopting the formula 5A for preparing to obtain a compound as shown in a formula 6A; f, reacting the compound as shown in the formula 6A and a compound as shown in a formula 10A for preparing to obtain a compound as shown in a formula 7A; g, adopting the compound as shown in the formula 7A for preparing to obtain the compound as shown in the formula 8A. According to the method provided by the invention, the compound 8 is synthesized through a brand new process route, and is then adopted as an intermediate for preparing Suvorexant, so that the problems of the usage of toxic substances, high cost, long route and low yield in an existing method for preparing the Suvorexant are effectively solved, and the method is suitable for industrial application.

A solid dispersion comprising suvorexant or a salt thereof in amorphous form and at least one pharmaceutically acceptable matrix compound, wherein the matrix compound is (i) a polymer and wherein the solid dispersion contains the suvorexant or salt thereof in an 5 amount of at least 50 weight-% based on the combined weight of the suvorexant or salt thereof and the at least one matrix compound, or (ii) a silicon-based inorganic adsorbent.

The present invention relates to pharmaceutical formulations comprising as active compound Suvorexant, or its salts, or its metabolites or derivatives, thereof and pharmaceutical excipients, process for the preparation thereof and pharmaceutical compositions containing them. The pharmaceutical formulations of the present invention possess instantaneous redispersibility, increased apparent solubility and permeability, no observable food effect with respect to immediate absorption and more predictable plasma concentration throughout the night and next morning. The invention also relates to methods of manufacturing the pharmaceutical formulations and pharmaceutical compositions containing them according to the invention, their uses and methods of treatments using the pharmaceutical formulations and their pharmaceutical compositions.

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.

The present invention discloses an imine reductase StIR (WP_023587323.1) derived from streptomyces thermolilacinus or an imine reductase KcIR (WP_020388085.1) from kribbella catacumbae or an imine reductase SiIR (WP_044567941.1) from streptomyces iranensis or an imine reductase LmIR (CAJ03998.1) from leishmania major strain friedlin or an imine reductase MsIR (WP_026609689.1) from methylocaldum szegediense or an imine reductase MbIR (WP_067084177.1) from microbulbifer, and the imine reductase is also used as a biological catalyst to prepare anti-insomnia drug suvorexant intermediate 5-chloro-2-((R)-5-methyl-[1,4] diazacyclic heptyl-1-yl)benzoxazole. The corresponding imine reductase can catalyze a substrate of 5-100 g/L and has a conversion rate more than 99%. The method has characteristics of mild reaction conditions, no pollution, simple process routes, etc., and has relatively great industrial application prospects.

The invention relates to the technical field of medicines, and provides a suvorexant tablet and a preparation method thereof, and the suvorexant tablet comprises 35-55 parts by weight of a suvorexant solid dispersion, 10-20 parts by weight of lactose, 30-50 parts by weight of microcrystalline cellulose, 11-20 parts by weight of a disintegrating agent and 0.5-3 parts by weight of a lubricant. According to the suvorexant tablet provided by the invention, the suvorexant is subjected to micro-powder treatment, the suvorexant and the copovidone are firstly prepared into the solid dispersion by adopting a hot melting process, and then the solid dispersion and various auxiliary materials are prepared into the tablet, so that the dissolution property of the indissolvable medicine suvorexant is improved, the absorption rate of the suvorexant in a human body is favorably improved, and the curative effect of the suvorexant is improved. Therefore, the bioavailability is improved.