Crystal form of deuterated osimertinib pharmaceutical salt and preparation method thereof

Abstract

The invention relates to a compound crystal form and a preparation method thereof, in particular to a crystal form I of a deuterated osimertinib pharmaceutical salt as well as a preparation method andapplication thereof. An X-ray powder diffraction pattern of the crystal form represented by a 2theta angle has characteristic diffraction peaks at positions of 5.49 +/-0.2 degrees, 6.42 +/-0.2 degrees, 11.01 +/-0.2 degrees, 11.61 +/-0.2 degrees, 12.46 +/-0.2 degrees, 13.42 +/-0.2 degrees, 14.22 +/-0.2 degrees and 15.58 +/-0.2 degrees. The crystal form is not easy to absorb moisture, has higher solubility, better stability, better fluidity and preparation processability, and has important significance in preparation of EGFR tyrosine kinase inhibitor drugs. The invention also discloses the preparation method of the crystal form I of the deuterated osimertinib pharmaceutical salt, and the crystal form I obtained by the preparation method has higher purity and higher yield.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a crystal form of a medicinal salt of deuterated osimertinib and a preparation method thereof. Background technique [0002] In my country, more than 730,000 new lung cancer patients are diagnosed every year, which is the malignant tumor with the highest morbidity and mortality. About 30% to 40% of non-small cell lung cancer patients in China have EGFR mutations, and patients with EGFR mutations who have received EGFR-TKI drugs (such as gefitinib, erlotinib, and icotinib) Among them, about two-thirds of patients will develop drug resistance due to the T790M mutation, leading to re-progression of the disease, and patients urgently need new treatment options. [0003] Osimertinib (generic name Osimertinib, hereinafter referred to as this) is the third-generation oral, irreversible and selective EGFR mutation inhibitor developed by AstraZeneca. Approved tumor drug for...

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Problems solved by technology

[0005] Chinese patent CN104140418A discloses 2-(2,4,5-substituted aniline) pyrimidine derivatives and their uses, through the selective deuteration of Osimertinib, the compound (structure shown in formula I ~ formula V) or its pharmaceutically acceptable The salt or solvate of the compound improves the pharmacokinetic properties of the drug and reduces the toxicity of the drug; however, the specific physical and chemical data such as the crystal form, hygroscopicity, and solubility of the compound are not disclosed, and other crystal forms and stability data of the compound are not reported.

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