34 results about "Cyanopyrazine" patented technology

The invention relates to a favipiravir intermediate and a synthetic method for favipiravir, and specifically discloses a method for synthesizing 3,6-difluoro-2-cyanopyrazine with a formula 4 as shownin the specification. The method comprises the following steps: a) allowing a compound with a formula 1 as shown in the specification to react with a chlorinated reagent or a brominated reagent so asto obtain a compound with a formula 2 as shown in the specification; b) allowing the compound with the formula 2 as shown in the specification to react with phosphorus oxychloride in the presence of organic base so as to obtain a compound with a formula 3 as shown in the specification; and c) allowing the compound with the formula 3 as shown in the specification to react with a fluorinated reagentso as to obtain the compound with the formula 4 as shown in the specification. The invention also relates to a method for synthesizing the favipiravir by using the above-mentioned method.

The invention provides modification and application of nitrile hydratase amino acid motif, and belongs to the technical field of bioengineering. According to the invention, nitrile hydratase derived from pseudonocardia thermophila is modified, the NO.46 site on a beta subunit and the NO.6 site and NO.126 site on an alpha subunit of a wild type are mutated respectively, and the specific enzyme activity of a constructed mutant is remarkably improved and can be improved by 1-5 times compared with that of the wild type. Moreover, the substrate spectrum is also broadened, the mutant has a very goodcatalytic effect on isobutyronitrile, n-valeronitrile, acrylonitrile, nicotinonitrile, 2-cyanopyrazine, benzonitrile, cinnamonitrile, naphthonitrile and the like, and the catalytic performance on corresponding substrates is also remarkably improved. Therefore, the obtained nitrile hydratase mutant can be suitable for more production scenes, and the production efficiency is improved.

The invention relates to a preparation method of 2-aminopyrazine derivatives, and belongs to the technical field of organic synthesis.With 2-cyanopyrazine as the raw material, by adding a sodium hypochlorite solution and alkali, 2-aminopyrazine is prepared through reaction, then 2-amino-3,5-dibromopyrazine is obtained through bromination reaction, and 2-amino-5-bromine-3-morpholinopyrazine, 2-amino-5-bromine-3-piperazinylpyrazine and 2-amino-5-bromine-3-pyrrolidylpyrazine are obtained after substitution reaction is conducted on 2-amino-3,5-dibromopyrazine as the raw material together with morpholine, piperazine and pyrrole respectively.With 2-cyanopyrazine as the raw material, different 2-aminopyrazine derivatives are prepared, the raw materials are low in price and easy to obtain, operation is easy, and target product yield is high.

The invention discloses a modified activated carbon carrier for immobilizing a phorate degradation bacterium. Activated carbon is washed and modified with a mixed liquid prepared from 3-chloro-6-phenyl pyridazine, alcohol, 4-(2-aminoethyl)-tetrahydropyrane, 2-bromo-5-cyanopyrazine and 5-chloro-3-methylbenzothiophene to prepare a substance B; the substance B is modified with a mixed liquid prepared from ZrCl4, CeCl3, Cu(NO3)2 and Sr(NO3)2 to prepare a substance C; and the substance C is modified with a mixed liquid prepared from 3-hydroxyflavone, alcohol, chlorphenyl silane and 2-imidazolidone to obtain a substance which is the modified activated carbon carrier for immobilizing the phorate degradation bacterium.

The invention relates to a refluxing improved rectifying tower for 2-cyanopyrazine. The refluxing improved rectifying tower comprises a tower body provided with an extraction hole, a plurality of pieces of tower plates and a refluxing system, wherein the refluxing system comprises an extraction pipe connected with the extraction hole, a heat exchanger connected with the extraction pipe and a refluxing main pipe connected with the heat exchanger; each tower plate comprises a hollow shell body, a plurality of sieve holes which are formed in the shell body and penetrate through the shell body, and a plurality of spraying holes which are formed in a non-sieve-hole region of the bottom surface of the shell body; a refluxing auxiliary pipe, which is communicated with the inner part of the shellbody and extends out of the tower body, is arranged on a side face of each tower plate; each refluxing auxiliary pipe is communicated with the refluxing main pipe and an auxiliary pipe valve is arranged on a pipe body; each sieve hole is internally provided with a sealing circular ring which is coaxial with the sieve hole and is fixedly connected with the shell body; a main pipe valve is arrangedat the tail end of the refluxing main pipe. According to the refluxing improved rectifying tower for the 2-cyanopyrazine, the characteristic that positions of the different tower plates correspond todifferent separation efficiency can be sufficiently utilized, so that the purification effect of single-time refluxing is remarkably improved and the refluxing time needed for reaching the effect is effectively shortened, and furthermore, the whole efficiency of refluxing operation is greatly improved.

A preparation process of pyrazinamide comprises the following steps: (1) synthesis of 2-methylpyrazine: putting a catalyst I into a reactor I, and performing reducing for 4 hours; adding 2-methylpyrazine into the reactor I, then adding ethylenediamine and 1, 2-propylene glycol, carrying out gas-solid phase contact catalytic reaction in the reactor I, cooling a mixture generated by the reaction through a condenser, feeding the mixture into a receiver, taking tail gas, and performing absorbing, emptying and separating to obtain 2-methylpyrazine, (2) chemical base catalysis; putting the catalystII into a reactor II, introducing an aqueous solution of 2-methylpyrazine in a mass ratio of (1:10)-(1:20) into the reactor II through a metering pump, introducing ammonia gas and air, controlling thetemperature of the reaction system to be 3-6 DEG C, maintaining the pH value to be 9-10, performing reacting for 1-2 hours, and performing heating to 20-30 DEG C to obtain 2-cyanopyrazine; and (3) synthesis of pyrazinamide. The preparation process of pyrazinamide has the advantages of the simple process, the high conversion rate, no generation of by-product pyrazinic acid, the good economic benefits and the wide application prospect.

The invention provides a refining method of favipiravir. The method specifically comprises the following steps: 6-fluoro-3-hydroxy-2-cyanopyrazine reacts with hydrogen peroxide under an alkaline condition to obtain 6-fluoro-3-hydroxy-2-pyrazinamide; the 6-fluoro-3-hydroxy-2-pyrazinamide is prepared into an organic alkali salt in an anhydrous organic solvent, and then the pH value in water is adjusted to prepare high-purity 6-fluoro-3-hydroxy-2-pyrazinamide; and 6-fluoro-3-hydroxy-2-pyrazinamide and organic alkali are salified in an organic solvent, the salt has excellent crystallinity, high-purity favipiravir can be prepared with high yield through simple operation, the yield can reach 90% or above, and the HPLC purity reaches 99.9% or above.

The invention discloses a preparation method of acetylpyrazine. Acetylpyrazine is prepared from 8-10 parts of magnesium chips, 180-200 parts of anhydrous tetrahydrofuran, 300-350 parts of chloromethane, 450-500 parts of anhydrous toluene, 20-25 parts of cyanopyrazine, 40-50 parts of alcohol, 2 parts of activated carbon and a plurality parts of chloromethane. Acetylpyrazine has the advantages that the synthesis method is simple, the raw materials are easy to obtain, energy consumption and material losses are low, the safety and the finished product content are high, and acetylpyrazine is suitable for large-scale production.

The invention discloses a microchannel reactor for 2-cyanopyrazine preparation. The microchannel reactor comprises a microchannel plate and a seal plate, the microchannel plate and the seal plate areoverlapped, and one surface, close to the seal plate, of the microchannel plate is provided with an etching groove. The etching groove fits the seal plate to form a microchannel, an inlet end of the etching groove is provided with a gasification groove, and the gasification groove are provided with a liquid inlet and a gas inlet to communicate with the outside. The microchannel reactor has advantages that the microchannel is formed by the seal plate and the microchannel plate with the etching groove, the inlet of the microchannel is provided with the gasification groove for mixing reaction materials, the middle of a reaction channel is filled with a catalyst, and reaction material gas and the catalyst are subjected to gas-solid reaction to synthesize a product; since the microchannel is small in flow through area but large in surface area, long-time mixing reaction of materials can be realized only through a small device while quick heat conduction can be realized, high safety is realized, catalysis is benefited, and accordingly reaction efficiency can be improved.

The invention provides an application of nitrile hydratase in catalyzing a hydration reaction of a cyanopyrazine compound to generate an amide pyrazine compound, and belongs to the technical field ofbiochemical engineering. The nitrile hydratase is derived from Agrobacterium tumefaciens, Stappia aggregata IAM 12614 or Sinorhizobium meliloti. The cyanopyrazine compound is used as a substrate, in-vitro nitrile hydratase or a cell expressing the nitrile hydratase is used as a catalyst, the hydration reaction is carried out, and the amide pyrazine compound can be obtained. The applied raw material is high in conversion rate and free of side reaction, and the product is easy to separate and purify and is relatively high in purity; and compared with a traditional chemical catalysis process, theprocess is environmentally friendly and easy and convenient to operate, and the yield exceeds 99%.

The present invention relates to a favipiravir intermediate 3, 6-dichloro-2-cyanopyrazine synthesis process, which is characterized in that the synthesis route is as follows as described in the specification. The cheap 2-chloropyrazine is used as the raw material, the product 3, 6-dichloro-2-cyanopyrazine can be obtained only through two-step reaction, the total yield is 55% or above, all the used reagents can be common reagents which can be purchased commercially, the production cost is reduced, and a synthesis process for large-scale industrial production of the 3, 6-dichloro-2-cyanopyrazine is achieved. According to the method disclosed by the invention, the synthesis process conditions are optimized, and particularly, the catalyst and the cocatalyst in the step (2) are selected, so that the yield and the purity of the product are further improved.

A process for preparing 2-cyanopyrazine by ammonia oxidizing method features use of a special catalyst VaTibPcDdEeOx, where V and Ti are primary catalyst and P, Fe, Ni, Co, Bi, Mn, Cr, Mo, Cu, Zn, Sn, B, K, Li and Mg are multicomponent catalyst. Its advantages are high activity, selectivity, output rate and purity and simple process.