35results about How to "Short route steps" patented technology

The invention belongs to the technical field of medical production, and particularly relates to a preparation method of parecoxib sodium. The invention aims to provide a synthesis method of parecoxib sodium, which has the advantages of short synthesis route, mild and controllable conditions and low cost and is simple to operate. By using 5-methyl-3,4-diphenylisooxazole as the initial raw material, chlorosulfonation, acylation and salification are carried out to synthesize the target product parecoxib sodium. The synthesis method provided by the invention has the characteristics of short route steps, mild and controllable conditions, small environmental pollution, higher yield and the like, and is simple to operate and suitable for industrial production.

The synthetic method of relugolix provided by the invention or its salt comprises taking 1-(dimethylamino)-3-(4-nitrophenyl)-2-acetone and cyanoacetate as starting materials, After condensation cyclization, alkylation reaction, Ullmann reaction, coupling reaction, Relugolix 4 free base form or salt form is obtained: this synthetic route optimizes the process, shortens the route steps, improves the route efficiency, and The use of precious metal catalysts can be reduced, which greatly reduces the process cost. The route is simple to operate, not only the total yield is high, but also the obtained product has high purity, which is suitable for scale-up production. We also found three salt forms of relugolix, which have better crystallinity and are easy to purify, which is beneficial to improve product purity.

The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of ambrisentan. In the preparation method, ambrisentan is prepared through benzyl protection reaction, condensation reaction and benzyl protection group removal reaction. Among them, the benzyl-protected intermediate is directly put into the next step of anti-condensation reaction without post-treatment; the debenzylation reaction adopts catalytic hydrogenation, which is green and environmentally friendly, and the reaction operation and post-treatment are simple. After being treated with ether solvent and beating, it can effectively remove the residual raw materials and impurities in the solid. intermediate, obtain the ambrisentan crude product, and then adopt the steps of recrystallization from methanol / water mixed solvent to obtain high-purity ambrisentan. The overall route has few steps and high yield, short production cycle, simple operation, good reproducibility and mild conditions, and is suitable for industrial production.

The invention provides a kind of preparation method of cariprazine, it comprises the steps: trans-2-(trans-4-(3,3-dimethylureido) cyclohexyl) derivative reacts in acid-binding agent Reaction with 1‑(2,3‑dichlorophenyl)piperazine or its salts under conditions, followed by reaction with reducing agent to generate cariprazine. The synthesis route of cariprazine of the present invention has few steps, simple process and meets production requirements.

The invention discloses a process method suitable for amplification preparation of 4-(6-aminopyridin-3-yl) substituted piperidine, and belongs to the synthesis field of a medicine intermediate. N-substituted piperidone, aryl sulfohydrazide and 2-amino-5-bromopyridine are subjected to a coupling reaction under a palladium catalyst, and then are subjected to a hydrogenation to obtain 4-(6-aminopyridin-3-yl) substituted piperidine. According to the process, the raw materials in pyridine do not need to be protected; the condensation and the coupling are carried out in the same reaction kettle, sothat the operation cost is reduced, the steps of performing protection at first and then performing protection removal as in documents can be avoided, and production cost of the existing biological, medicine and chemical intermediates is greatly reduced; and the process is subjected to amplification verification in kilogram-scale, and the verification proves that the yield and the product purity are basically equal to those of gram-scale, so that the method can be used as a process for industrial scale production.

The invention discloses a synthetic 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide intermediate (compound I) and its The preparation method and application include the following steps: using 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (compound II) as a starting material, first preparing compound III by applying a protecting group; compound III Compound IV is obtained through carbonyl insertion reaction; compound V is obtained through deprotection group; compound VI is obtained by selective dechlorination; compound I is obtained by cyclopentyl on compound VI; compound VI is obtained by hydrolysis of compound I; -7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (Compound VIII).

The invention discloses a preparation method of odancati and its intermediate. The invention provides a preparation method of trifluoroacetophenone biphenylmethyl sulfone intermediate I, comprising the following steps: in a solvent, in the presence of a metal catalyst and an inorganic base, 2,2,2-trifluoroacetophenone- 4-boronic acid pinacol ester and 4-bromophenyl methyl sulfone carry out coupling reaction, obtain trifluoroacetone biphenyl methyl sulfone intermediate I. The preparation method of the present invention has the advantages of simple and safe operation, short route steps, environmental friendliness, high reaction yield, and high purity of the prepared product, and is prepared by using the trifluoroacetone biphenylmethyl sulfone intermediate I of the present invention as an intermediate Odangcati II has high purity, meets the standards of raw materials, and is suitable for industrial production.

The invention discloses a preparation method of ezetimibe and an intermediate thereof. The invention provides a preparation method of ezetimibe intermediate IV, comprising the following steps: in an organic solvent, in the presence of a trialkylchlorosilane, an organic base, a chiral catalyst and lithium diisopropylamide, the ezetimibe The ezetimibe intermediate II and the ezetimibe intermediate III undergo a ring closure reaction to obtain the ezetimibe intermediate IV; R is methyl, ethyl or propyl. The preparation method of the present invention has short route steps, mild reaction conditions, simple post-treatment steps, avoids substrates connected with chiral groups, and the prepared product has high purity, meets the standard of raw materials, high yield, low production cost, and atom utilization High efficiency, suitable for industrial production.

The invention discloses a method for synthesizing cis-1,4-cyclohexanediol, which belongs to the field of organic chemical synthesis. The method uses 4-(hydrocarbyl acyloxy)cyclohexanone as a raw material, and only undergoes reduction and hydrolysis. cis-1,4-cyclohexanediol can be easily synthesized. The method can ensure high selectivity of the reaction, and the obtained product yield is high, and is suitable for large-scale production.

The invention discloses a preparation method of 1,1-diphenylethylene shown in a formula (V). The method comprises the steps of firstly carrying out reaction on bromobenzene and magnesium chips in anhydrous 2-methyltetrahydrofuran to obtain a phenylmagnesium bromide Grignard reagent, and then dripping acetophenone into the phenylmagnesium bromide Grignard reagent to react, so as to generate 1,1-diphenylethanol; finally, dewatering 1,1-diphenylethanol in the presence of a sulfoacid functional ionic liquid catalyst, so as to obtain 1,1-diphenylethylene shown in the formula (V). The preparation method disclosed by the invention is short in reaction step, mild in condition, simple and convenient to operate, high in product yield, low in production cost, friendly to environment, and applicable to industrial production.

The invention discloses a preparation method of pramipexole dihydrochloride and an intermediate thereof. The invention provides a preparation of pramipexole II. The preparation method of the pramipexole II comprises the following steps: performing condensation reaction and reduction reaction on a pramipexole intermediate III, propylamine and hydrogen in an organic solvent and under the existence of a chiral catalyst, and performing one-pot method to obtain the pramipexole II. According to the preparation method provided by the invention, the route step is short, chiral resolution is not neededand the total molar yield is high; furthermore, the prepared product has high purity, can reach to the standard of raw material medicines and is suitable for industrialized production. (The formula is shown in the description).