50 results about "Eltrombopag" patented technology

The invention provides a preparation method of an eltrombopag tablet, belongs to the field of medicine new technologies, and relates to the eltrombopag tablet and the preparation method of the eltrombopag tablet. Eltrombopag serves as the main component of the tablet, and the tablet can be used for treating skin and skin tissue infection caused by gram-positive bacteria.

The invention provides a method for preparing a compound shown as the formula I (please see the formula in the description). The method specifically comprises the following steps that 1, a compound shown as the formula (II) (please see the formula in the description) reacts with a compound shown as formula (V) (please see the formula in the description) under the alkaline condition to generate a compound shown as the formula (III) (please see the formula in the description); 2, the compound shown as the formula (III) (please see the formula in the description) reacts with a compound shown as the formula (VI) (please see the formula in the description) under the alkaline condition in the presence of palladium carbon to generate a compound shown as the formula (IV) (please see the formula in the description); 3, the compound shown as the formula (IV) (please see the formula in the description) reacts in the presence of palladium carbon and a hydrogen source under the alkaline condition to generate the compound shown as the formula (I) (please see the formula in the description). According to the method, design is ingenious, protecting group removal, dechlorination and nitro reduction are together completed in the final hydrogenation process, and the purity of the obtained compound shown as the formula (I) (please see the formula in the description) is high; the most important thing is that compared with other Suzuki coupling agents, cost of palladium carbon is lower, a source of palladium carbon is wide and easy to obtain, palladium carbon can be directly recycled and reused after being simply filtered and separated, and therefore the material cost is greatly reduced; meanwhile, emission of three wastes is reduced, and the method is quite suitable for industrialized production.

The invention provides a preparation method of eltrombopag diethanolamine salt; the preparation method is simple to perform and suitable for industrial production; active pharmaceutical ingredients of the eltrombopag diethanolamine salt prepared herein meet provisions in ICH (international council for harmonisation) guidelines.

The invention is named as a method for detecting related substances of Eltrombopag intermediate I, and belongs to the technical field of drug analysis. The present invention respectively adopts chromatographic columns with phenyl and octadecylsilane bonded silica gel as fillers, uses phosphate buffer solution and acetonitrile or phosphate acetonitrile solution as mobile phase, adopts gradient elution mode, and establishes two high-efficiency The liquid phase analysis method can effectively determine Eltrombopag synthetic intermediate Ⅰ 2'-hydroxy-3'-amino-biphenyl-3-carboxylic acid and intermediate Ⅱ 2-(3,4-dimethyl-phenyl) ‑5‑methyl‑2,4‑dihydro‑pyrazole‑3‑one and the content of related impurities in the above-mentioned intermediates, the method has good specificity, high sensitivity, and convenient operation. effective guarantee. The invention also discloses a new impurity reference substance compound.

The invention provides a method for preparing a compound shown as the formula I (please see the formula in the description). The method specifically comprises the following steps that 1, a compound shown as the formula (II) (please see the formula in the description) reacts with a compound shown as formula (V) (please see the formula in the description) under the alkaline condition to generate a compound shown as the formula (III) (please see the formula in the description); 2, the compound shown as the formula (III) (please see the formula in the description) reacts with a compound shown as the formula (VI) (please see the formula in the description) under the alkaline condition in the presence of palladium carbon to generate a compound shown as the formula (IV) (please see the formula in the description); 3, the compound shown as the formula (IV) (please see the formula in the description) reacts in the presence of palladium carbon and a hydrogen source under the alkaline condition to generate the compound shown as the formula (I) (please see the formula in the description). According to the method, design is ingenious, protecting group removal, dechlorination and nitro reduction are together completed in the final hydrogenation process, and the purity of the obtained compound shown as the formula (I) (please see the formula in the description) is high; the most important thing is that compared with other Suzuki coupling agents, cost of palladium carbon is lower, a source of palladium carbon is wide and easy to obtain, palladium carbon can be directly recycled and reused after being simply filtered and separated, and therefore the material cost is greatly reduced; meanwhile, emission of three wastes is reduced, and the method is quite suitable for industrialized production.

The invention discloses a preparation method of eltrombopag. The preparation method comprises the following steps: 1, sequentially and continuously reacting a starting material I, glacial acetic acid and hydrobromic acid to obtain an intermediate I; 2, reducing the intermediate I through ammonium formate under the catalytic action of palladium to obtain an intermediate II; and 3, carrying out diazotization addition on the intermediate II to obtain eltrombopag. According to the method, on the premise of ensuring the medicine quality, direct reduction of nitryl by hydrogen is avoided, so that safe production amplification can be realized. Meanwhile, on the basis that the single maximum impurity of eltrombopag is controlled not to exceed 0.1% and the total impurity is controlled not to exceed 1.0%, the reaction can be completed more quickly, the time of the preparation process can be further shortened, the preparation speed of eltrombopag is increased, and the market competitiveness of the eltrombopag is enhanced.

The application discloses a synthetic method of an eltrombopag intermediate, comprising: subjecting 2-aminophenol derivative shown as formula (II) as a raw material to react with an aromatic reagent shown as formula (III) to obtain an intermediate product shown as formula (IV); using the intermediate product shown as formula (IV) as a raw material to prepare the eltrombopag intermediate shown as formula (I), wherein R1 is selected from amino derivatives, and R2 is selected from halogen and sulfonyloxy group. The synthetic method has few reaction steps; the starting material is simple; the synthetic method is simpler, more economical and greener.

The invention relates to the technical field of medicine preparation, and discloses an eltrombopag diethanolamine salt and a preparation method thereof. The preparation method comprises the followingsteps: dissolving ethanolamine in an organic solvent; heating to 60-75 DEG C, stirring to dissolve ethanolamine, dropwise adding a tetrahydrofuran solution of eltrombopag free acid into the ethanolamine solution, keeping the temperature, stirring, cooling after dropwise adding, and filtering, wherein the volume ratio of tetrahydrofuran to eltrombopag free acid to the organic solvent is (6-11): 1:(12-24). According to the method, in a homogeneous reaction system, sufficient salification is guaranteed, and the prepared eltrombopag diethanolamine salt is low in impurity content, simple in reaction operation, suitable for amplification and suitable for industrial production.

The present invention relates to an improved process for the purification of Eltrombopag olamine of compound of formula (2). The present invention also relates to an improved process for the preparation of Eltrombopag olamine intermediates and further conversion to Eltrombopag olamine of a compound of formula (2).