Preparation method of N-(4-(3-amino-1H-indazol-4-yl) phenyl)-N'-(2-fluoro-5-methylphenyl) urea and intermediate thereof

Abstract

The invention provides a preparation method of N-(4-(3-amino-1H-indazol-4-yl) phenyl)-N'-(2-fluoro-5-methylphenyl) urea and an intermediate thereof. Specifically, the invention provides a preparation method of a borate ester compound as shown in a formula I, and the preparation method comprises the following steps: enabling a compound as shown in a formula III to react with a compound as shown in a formula IV to generate a compound as shown in a formula V, and enabling the compound as shown in the formula V to react with a boron reagent to generate the compound as shown in the formula I. The method has the characteristics of convenience in reaction, easiness in obtainment of the intermediate, high yield, high product purity of above 98.5%, low cost of raw materials and the like, and is suitable for industrial application.

Description

technical field

[0001] The invention belongs to the field of drug synthesis, in particular, the invention relates to a kind of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N′-(2-fluoro-5-methyl The preparation method of phenyl) urea and its intermediate borate ester compound. Background technique

[0002] Angiogenesis is a physiological process in which capillaries grow out of the existing vascular network, which can meet the nutrient supply during tissue generation and is essential for the maintenance or growth of tumors. Therefore, angiogenesis inhibitors are considered to be effective in cancer treatment. means. The receptor tyrosine kinase (RTK) of vascular endothelin plays an important role in the process of angiogenesis and can be used as the target of antitumor drugs.

[0003] Abbott has developed a series of RTK inhibitors (WO2004113304A1), including indazole, benzisoxazole and benzisothiazole kinase inhibitors, which specifically inhibit all vascular endothelial growth f...

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