41 results about "4-cyanopyridine" patented technology

The invention belongs to the field of medicine and chemical engineering, and particularly discloses a preparation technology for 5-(2-cyano4-pyridyl)-3-(4-pyridyl)-1,2,4-troazole (topiroxostat). The preparation technology is characterized in that methyl isonicotinate serving as a compound II is used as a starting raw material, the compound II, phosphorus oxychloride, N,N-dimethyl formamide, iodine and 28% ammonium hydroxide form a compound III which is 2-cyano methyl isonicotinate in a one-pot synthesis mode, then a compound IV which is 2-cyano isonicotinyi hydrazine is formed through synthesis, a topiroxostat crude product Ia is prepared through condensing the compound IV which is 2-cyano isonicotinyi hydrazine and 4-cyanopyridine, salifying is performed on the crude product Ia and para-toluenesulfonic acid to form topiroxostat tosilate Ib, and finally the topiroxostat finished product I is obtained through desalting in a refined mode. The number of reactions steps is reduced, the yield of the finished product is increased, the reaction process is low in toxin and has small influences on environment, the reaction route is short, the cost is greatly lowered, the product purity is larger than 99.7%, the net contamination is smaller than 0.1%, and standard requirements are met.

The invention provides a preparation method of topiroxostat. The preparation method comprises the steps that 2-cyano methyl isonicotinate is used as raw materials; hydrazinolysis is performed at -10 DEG C to -20 DEG C to obtain an intermediate; the intermediate and 4-cyanopyridine react under the conditions with sodium ethoxide and the pH being 4 to 6 to obtain the topiroxostat. The preparation method has the advantages that the 2-cyano methyl isonicotinate is used as a starting material; the 2-cyano methyl isonicotinate and hydrazine hydrate take condensation reaction at low temperature to prepare the intermediate; the intermediate and the 4-cyanopyridine are subjected to condensation and loop closing under the acid condition with sodium ethoxide to prepare the topiroxostat. The raw materials can be easily obtained; the reaction conditions are mild and are easy to control; a reagent with high toxicity is not used in the reaction process; the released toxic substances are few; the sidereaction products are few; the reaction safety is high; the pollution is small; the obtained purity is high; the preparation method is suitable for industrial production.

The invention discloses a preparation method of 4-pyridylaldehyde, which belongs to the field of heterocyclic compounds, and comprises the following steps of: (1) adding 4-cyanopyridine into protonic acid water solution, adding a Cu-Ni catalyst, mixing uniformly, and adding hydrogen to carry out hydrogenation reaction until finishing the reaction; (2) filtering; (3) adding a neutralizing agent into the obtained 4-pyridylaldehyde acid solution filtered through the step (2), and neutralizing until a pH value reaches 4-6; and (4) separating and purifying the 4-pyridylaldehyde. According to the method, the Cu-Ni catalyst is adopted to carry out catalytic hydrogenation, so that the generation of 4-pyridinemethylamine, 4-pyridinemethanol and other impurities is avoided, the reaction period is short, and the yield and the purity are high.

The invention discloses a high performance liquid chromatographic detection method for 3-cyanopyridine and 4-methylpyridine in 4-cyanopyridine. The high performance liquid chromatographic detection method comprises the following steps: (1) preparing a system applicable solution; (2) preparing a test solution; 3) preparing a contrast solution. The system applicable solution, the test solution and the contrast solution are detected respectively by adopting high performance liquid chromatography. The detection condition is as follows: octadecylsilane chemically bonded silica is used as a filling agent of a chromatographic column; a mobile phase A is modified buffer salt, and is prepared by adding 20 mmol of potassium dihydrogen phosphate and 2.4 ml of triethylamine into 1000 ml of water and adjusting the pH value to 6.0-8.0 with phosphoric acid; a mobile phase B is an organic phase, and adopts gradient elution; the flow rate is 0.5-1.5 ml / min; the column temperature is 10-40 DEG C; the detection wave length is 200-300 nm; the injected sample volume is 10 [mu]l. The separation degree of 3-cyanopyridine, 4-cyanopyridine and 4-methylpyridine in the detection method are all 2.0 or above, the theoretical plate number is high, the symmetry is good, and the condition that the accuracy of the detection results is influenced by interference between the components is effectively avoided; meanwhile, the detection method has the advantages of being accurate and reliable in detection result, short in analysis time, simple and convenient to operate, and the like.

The invention belongs to the field of medicine and chemical industry and discloses a synthesis method of topiroxostat. The method comprises that 4-cyanopyridine as a starting raw material is oxidized by hydrogen peroxide to form an intermediate 1, the intermediate 1, sodium methoxide and ammonium chloride undergo a reaction to produce an intermediate 2, the intermediate 2 and 4-cyanopyridine undergo an annulation reaction under action of cuprous bromide and sodium carbonate to produce an intermediate 3, and the intermediate 3 and trimethylsilyl cyanide undergo a cyanation reaction to produce topiroxostat. The method utilizes low-price 4-cyanopyridine as a starting raw material, and in the first reaction step, methanol is used as a solvent and 4-cyanopyridine nitrogen oxide as the intermediate 1 is prepared. The method has a high yield and produces a high-purity product. The whole route is easy to operate and is conducive to industrial mass production.

The invention provides a synthesis method of 2-(4-cyano) pyridyl (3-cyano) thioanisole. The invention also provides a synthesis method of 4-(2-formamido) pyridyl (3-bromo) thioanisole. According to the technical scheme, 2-chloro-4-cyanopyridine / 4-chloropyridine-2-formamide, micromolecular sulfur compounds and 3-chloro / bromobenzyl alcohol are used for directly synthesizing 2-(4-cyano) pyridyl (3-cyano) thioanisole (I) and 4-(2-formamido) pyridyl (3-bromo) thioanisole (II) under the condition of no additional catalysts. The method has the advantages that the reaction conditions are simple; inert gas protection is not needed; solvents are not needed; the operation is easy. By the method, the 20-time amplification production can be conveniently realized; the product gram grade preparation is performed, so that certain study and industrial application prospects are realized.

The invention discloses a myricetin pharmaceutical eutectic crystal and a preparation method thereof. The myricetin pharmaceutical eutectic crystal uses myricetin as the active pharmaceutical ingredients, uses theine, nicotinamide, pyrazinamide or 4-cyanopyridine as the precursors, and is a myricetin-theine eutectic crystal, a myricetin-nicotinamide eutectic crystal, a myricetin-pyrazinamide eutectic crystal or a myricetin-4-cyanopyridine eutectic crystal formed through intermolecular hydrogen bonds. The eutectic crystals are prepared by adopting the solution mediating crystal transformation method. The myricetin pharmaceutical eutectic crystal provided by the invention inherits the pharmacological activity of the myricetin; meanwhile, the solubleness, the dissolution rate and the stability of the myricetin pharmaceutical eutectic crystal are all significantly improved as compared with those of the myricetin; the myricetin pharmaceutical eutectic crystal facilitates the development of pharmaceutic preparation and the wide applications of the myricetin in the field of medicine.

The invention belongs to the field of medicine and chemical industry, and specifically discloses a preparation of 5-(2-cyano4-pyridyl)-3-(4-pyridyl)-1,2,4-triazole (topinostat) The process is characterized in that the compound III 2-cyano group is synthesized by a one-pot method using compound II methyl isonicotinate as a starting material and phosphorus oxychloride, N,N-dimethylformamide, iodine simple substance, and 28% ammonia water Methyl isonicotinate, then compound IV 2-cyanoisonicotinic acid hydrazide is synthesized, and then compound IV2-cyanoisonicotinic acid hydrazide is condensed with 4-cyanopyridine to prepare topinostat crude product Ia, and crude product Ia is passed through with p-toluene After the sulfonic acid is salified, topinastat p-toluenesulfonate Ib is formed, and finally desalted and refined to obtain the finished product I of topinostat. The invention reduces the reaction steps, improves the yield of finished products, has low toxicity in the reaction process, has little impact on the environment, has a short reaction route, and greatly reduces the cost.

The invention discloses a synthesis method of 4-cyanopyridine, which is characterized in that 4-methylpyridine is vaporized and mixed with ammonia and air; the 4-methylpyridine reacts with the ammonia and air in the presence of a catalyst, and then the finished product of 4-cyanopyridine is obtained after absorption, extraction and rectification. The method features simple process and easy operation; the conversion rate of the 4-methylpyridine is more than 99% and the yield of the 4-cyanopyridine is more than 98%.

The invention discloses a new bacterial strain CGMCC3830 (Pseudomonas putida) and a method for catalytically producing nicotinic acid or isonicotinic acid by using the bacterial strain. In the invention, the nicotinic acid or isonicotinic acid is obtained through a hydrolysis reaction, wherein 3-cyanopyridine and 4-cyanopyridine are taken as raw materials, and the CGMCC3830 (Pseudomonas putida) with high nitrilase activity obtained through fermentation culture is taken as a catalyst. The method comprises the following steps of: adding a substrate in a reactor in a flowing mode, and reacting for 6-10 hours to obtain 147g / L-221g / L of nicotinic acid or isonicotinic acid. The CGMCC3830 (Pseudomonas putida) has the characteristics of short life cycle, strong vital force, high conversion efficiency, short conversion cycle and the like, the production cost of nicotinic acid or isonicotinic acid is reduced greatly. The production process has the characteristics of mild reaction conditions, low energy consumption and high yield, is environmentally-friendly and the like.