57 results about "Sitagliptin Phosphate" patented technology

The present invention is directed to a novel polymorph form of crystalline sitagliptin phosphate, named as Form V herein. The present invention further provides processes for preparations of Form V, pharmaceutical composition comprising Form V and its use in therapy. Form V can be prepared from recrystallizing sitagliptin phosphate in a mixture of methanol and water, a mixture of acetone and water, or from distillation of a mixture of organic solvents and water followed by recrystallization in the remaining aqueous solution.

The invention discloses a novel method for synthesizing sitagliptin phosphate and a derivative thereof. The method has the advantages of readily-available raw materials, mild reaction condition, no need of using very expensive catalyst, easy control over optical purity and the like. In the novel method for synthesizing sitagliptin phosphate and the derivative thereof, L-aspartic acid is taken as a raw material, and the chemical reaction steps of amino protection, esterification, reduction, iodination or bromination, coupling, hydrolysis, acylation ammoniation, removal of protecting groups andsalt formation are performed to obtain a sitagliptin phosphate chiral salt and a hydrate thereof. The method comprises the following specific steps of: performing amino protection, esterification, reduction and iodination on L-aspartic acid serving as the raw material to obtain a compound A shown as a formula I; undergoing a coupling reaction on the compound A and a compound B shown as a formula II to obtain a compound C shown as a formula III; and performing hydrolysis, acylation ammoniation, removal of protecting groups and a salt-forming reaction on the compound C to obtain a sitagliptin phosphate hydrate.

The invention relates to a synthesis method of a sitagliptin phosphate intermediate, and belongs to the technical field of organic synthesis. The method comprises the following technological steps of synthesizing a reaction liquid of 5-hydroxyl-[(2,4,5-trifluoro-phenyl)-ethylidene]-dimethyl-[1,3] dioxo-4,6-diketone from 2,4,5-trifluoro-phenylacetic acid, meldrum's acid, N,N-diisopropylethylamine, DMAP and acetylchloride; adding 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4] triazol [4,3-alpha] pyrazine hydrochloride and trifluoroacetic acid to obtain the product. According to the method, the reaction raw materials are easily available; the reaction process is simple in operation; the requirements on reaction equipment are low; the reaction conditions are relatively mild; the yield and content are high, the quantity of waste water and solid wastes is relatively low, the cost is saved, and the method is suitable for industrial production.

The invention discloses a dry granulation process for a sitagliptin phosphate composition, which includes the following steps: 1) selecting a phosphate liptin bulk drug with needle-like or rod-like shape; 2) premixing microcrystalline cellulose, west phosphate Gliptin and anhydrous calcium hydrogen phosphate are mixed and sieved, and then sieved croscarmellose sodium and sodium stearyl fumarate are added for blending; 3) granulation, and the final step in step 2). The mixture is prepared into granules by a dry granulator; 4) The material obtained from granulation is mixed with the sieved magnesium stearate. The needle-like or rod-like crystal habit has a larger specific surface area and is more prone to API inconsistencies. In a stable situation, with the addition of sodium stearyl fumarate in the granules, it is beneficial to accelerate the disintegration rate of the tablet. After the dry granules are prepared, most of sitagliptin phosphate has been wrapped in the dry granules, and then When mixed with magnesium stearate, the contact area between API and magnesium stearate is greatly reduced, ensuring the stability of the finished product.