Preparation method of SGLTs inhibitor and key intermediate thereof

Abstract

The invention relates to a preparation method of an SGLTs inhibitor and a key intermediate of the SGLTs inhibitor. The SGLTs inhibitor is (1S, 2S, 3S, 4R, 5S)-5-(3-((2, 3-dihydrobenzo [b] [1, 4] dioxin-6-yl)methyl)-4-ethyl phenyl)-1-(hydroxymethyl)-6, 8-dioxabicyclo [3.2.1] octane-2, 3, 4-triol. According to the preparation method, 6-(2-ethyl-5-iodobenzyl)-2, 3-dihydrobenzo [b] [1, 4] dioxin is taken as a raw material, silyl is taken as a protecting group, and six-step reaction is carried out to prepare the product. The preparation method disclosed by the invention is simple to operate, high in yield of each step and stable in process, can adapt to industrial production requirements, solves the problem of drug accessibility, and is beneficial to acceleration of clinical development of the SGLTs inhibitor and drug marketing.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of an SGLTs inhibitor and a key intermediate thereof. Background technique [0002] Diabetes mellitus is a metabolic disorder characterized by recurrent or persistent hyperglycemia. In the early stage of diabetes treatment, diet control and exercise therapy are the first choice for blood sugar control. When these methods are difficult to control blood sugar, insulin or oral hypoglycemic drugs need to be used for treatment. Studies have found that the regulation of glucose transport by cells is mainly achieved by two protein family members, glucose-stimulating transporters (GLUTs) (passive transport) and sodium-dependent glucose co-transporters (SGLTs) (active transport). Among them, members of the SGLTs family with glucose transport function are mainly distributed in the proximal tubules of the intestine and kidney, and it is inferred that they pla...

AI Technical Summary

Problems solved by technology

In Example 9 of the patent application WO2015 / 032272A1, a preparation method of a compound of formula (A) is disclosed. The preparation method uses 2-bromo-5-iodobenzoyl chloride as a raw material, and first undergoes a three-step reaction to obtain 6-(2 -Ethyl-5-iodobenzyl)-2,3-dihydrobenzo[b][1,4]dioxin (compound of formula (1)), and then with compound of formula (1) as raw material, The compound of formula (A) is prepared through ten steps of reaction, wherein four kinds of protecting groups (trimethylsilane, tert-butyldimethylsilyl, acetyl and benzyl) are used for protection to prepare multichiral compounds, exceeding Half of the preparation steps need to use column chromatography, which is not conducive to industrial production. In addition, the yield of the penultimate aldehyde group reaction is only 16.6%, which has become a serious technical defect of the preparation process

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