Synthesis method of impurity of C-glycoside derivatives

Abstract

The invention relates to the technical field of medicinal chemistry, and particularly discloses a synthesis method of an impurity of C-glycoside derivatives. The impurity is a compound as shown in a formula (I) and is synthesized by the following steps: (1) dissolving a compound as shown in a formula (II) in ethyl acetate, and adding TEA and DMAP; dropwise adding acetic anhydride to prepare an intermediate 1 as shown in a formula (III); (2) adding the intermediate 1 into acetonitrile, and dropwise adding boron trifluoride diethyl etherate; dropwise adding a dichloromethane solution of a compound as shown in a formula (IV) for reaction to prepare an intermediate 2 as shown in a formula (V); (3) dissolving the intermediate 2 in methanol and tetrahydrofuran, and adding lithium hydroxide monohydrate for reaction; spin-drying a solvent, adding ethyl acetate for extraction, backwashing an organic phase with water and a saturated salt solution, adding anhydrous sodium sulfate for drying, and spin-drying; and carrying out column chromatography to separate the residues and spin-drying to obtain the compound as shown in the formula (I). The method provided by the invention solves the problem of large-scale production required by reference substances, improves the reaction yield and reduces the production cost.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a method for synthesizing impurities of C-glycoside derivatives. Background technique [0002] Hyperglycemia is considered a major risk factor for the development of diabetic complications and may be directly related to impaired insulin secretion in advanced type 2 diabetes. Normalization of insulin can therefore be expected to improve blood glucose in patients with type 2 diabetes. Most of the existing diabetes drugs are insulin secretory drugs or insulin sensitizers, such as sulfonylureas, glinides, thiazolidinediones, and metformin, which have potential side effects, such as easy to cause weight gain , hypoglycemia, lactic acidosis, etc. Therefore, there is an urgent need to develop novel, safe and effective antidiabetic drugs with a mechanism of action. [0003] In the kidney, glucose is freely filtered from the glomerulus (approximately 180 g / day), but is almos...

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Problems solved by technology

At present, there is no research on the impurities related to the C-glycoside derivatives represented by the formula (VI) in the above ZL201410004395.2 patent, and the compound represented by the formula (I) of the present invention is the applicant's research on the above-mentioned C-glycoside derivatives. An impurity component found in the synthesis process of C-glycoside derivatives, produced by the raw material represented by formula (II) and the product represented by formula (VI) under the catalysis of the reaction reagent boron trifluoride (Lewis acid) ,like figure 1 shown

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