32 results about "Idelalisib" patented technology

A preparing method of Idelalisib (I) is disclosed. The preparing method includes following steps of: subjecting R-2-hydroxybutyrate (II) and 6-amino-9H-purine to nucleophilic substitution under actions of a leaving agent and an acid-binding agent to produce an intermediate S-2-(N-9H-purin-6-yl)aminobutyrate (III); subjecting the intermediate (III) and 2-amino-6-fluorobenzoic acid to amidation under actions of a catalyst to produce S-2-(N-9H-purin-6-yl)amino-N-(2-carboxyl-3-fluorophenyl)butyramide (IV); subjecting the intermediate (IV) to a cyclization reaction in acetic anhydride; and performing a substitution reaction with phenylamine to obtain the Idelalisib (I). The preparing method has characteristics of easily available raw materials, simple and concise process, capability of being economical and environmental friendly, and suitability for industrial production.

The invention relates to idelalisib crystal, a pharmaceutical composition comprising the idelalisib crystal, and a preparation method and application of the idelalisib crystal, and belongs to the technical field of pharmaceutical composition crystals. The invention particularly provides crystal R; under Cu-KAlpha irradiation, the crystal R has X-ray powder diffraction spectrum substantially shown as in figure 1, 2 or 9. The preparation method of the crystal R is simple, the form of the crystal is easy to control, production efficiency is significantly increased, and the crystal R is more suitable for industrial production. The crystal has improved hygroscopicity, chemical stability and preparation adaptability, as well as improved efficacy and safety.

The invention relates to an o-fluoro-o-iminobenzoic acid intermediate compound and a preparation method and application thereof, belonging to the technical field of pharmaceutical intermediate synthesis. In order to solve the existing problems of difficult separation and poor activity, an intermediate compound of o-fluoro-o-iminobenzoic acid and its preparation method and application are provided. The method comprises dissolving the compound of formula II in an organic solvent, and then adding pyridine Stir with triphenyl phosphite to activate the carboxyl group, add 2-amino-6-fluorobenzoic acid for condensation reaction, and obtain the corresponding intermediate compound of o-fluoro-o-iminobenzoic acid. The intermediate compound of the present invention has high reactivity and is easy to be active, can be effectively applied to the key intermediate raw material for synthesizing Idelalisib, and has high reaction stability, and the obtained corresponding intermediate product also has the effect of high quality and purity.

The invention discloses a preparation method of Idelalisib and an intermediate thereof. The method comprises the following steps: using 2-halogeno-6-fluorine-N-phenyl benzamide as a raw material, performing a reaction on the 2-halogeno-6-fluorine-N-phenyl benzamide and N-(9'-tetrahydropyrane-6'-purinyl)-L-2-aminobutyric acid, performing a reaction on a reaction product and ammonium carbonate or liquid ammonia to replace 2-halogeno with ammonia by cuprous oxide, copper and potassium carbonate or cesium carbonate, performing a ring-closure reaction under the existence of hexamethyl disilazane and iodine, and performing a reaction on a reaction product and hydrochloric acid solution to remove pyran finally, so as to generate an Idelalisib finished product. According to the process, the novelmethod is provided for synthesizing the Idelalisib; in the process, the easily available 2-halogeno-6-fluorobenzoic acid is used as a starting material, and zinc acetate pollution and the like can beprevented from being generated through reduction of nitro and the like with zinc powder in a synthesis process.