The synthetic method of diazoxide

Abstract

The invention relates to a synthetic method of diazoxide (I). The synthetic method comprises the following steps of (a) carrying out catalytic hydrogenation reduction on 5-chlorine-2-nitrobenzenesulfonamide (II) in a solvent A through raney nickel so as to obtain 5-chlorine-2-aminobenzenesul fonamide (III), wherein the reduction reaction temperature ranges from 20 to 40 DEG C, the reduction reaction pressure ranges from 3 to 10kg / cm<2>, and the reduction reaction time ranges from 3 to 5 hours; (b) acetylizing the 5-chlorine-2-aminobenzenesul fonamide (III) in a solvent B through an acylation reagent with the existence of an inorganic substance acid-binding agent, carrying out ring-closure reaction on a product in a high-boiling-point inert solvent C, and obtaining a diazoxide (I) crude product, wherein the acetylation reaction temperature ranges from 0 to 30 DEG C, the acetylation time ranges from 2 to 10 hours, the ring-closure reaction temperature ranges from 240 to 250 DEG C, and the ring-closure reaction time ranges from 0.5 to 1.5 hours; (c) refining the diazoxide (I) crude product through ethyl alcohol with the concentration being 80 percent, and obtaining a diazoxide (I) finished product.

Description

technical field [0001] The present invention relates to the synthesis method of diazoxide. Background technique [0002] Diazoxide chemical name: 5-chloro-3-methyl-2 H -1,2,4-benzothiazine-1,1-dioxide, molecular formula: C 8 h 7 ClN 2 o 2 S, molecular weight: 230.67, chemical structure as follows: [0003] [0004] Diazoxide was first developed and synthesized by Schering in 1961. Diazoxide can relax vascular smooth muscle, reduce peripheral vascular resistance, cause a sharp drop in blood pressure, and inhibit pancreatic β cells from secreting insulin; clinically, it is mainly used for hypertensive crisis. Treatment of first aid for elephants, idiopathic hypoglycemia in young children, and severe hypoglycemia due to islet cell tumors. [0005] The synthesis method of diazoxide reported in the world has: U.S. Patent 2986573 uses 5-chloro-2-nitrobenzenesulfonamide as the starting material, and first reduces it with iron powder to generate 5-chloro-2-aminobenzenesulfo...

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Problems solved by technology

[0006] All of the above synthetic routes have major disadvantages: U.S. Patent 2986573 uses iron powder for reduction, which is labor-intensive and inefficient, and also produces a large amount of difficult-to-handle iron sludge, which pollutes the environment; and uses orthoacetic acid in the cyclization step Triethyl ester, low reaction yield, many by-products, difficult purification, low product quality

U.S. Patent 3345365 uses acetic anhydride / pyridine as the acetylation reagent, which will produce a large amount of acetic acid-pyridine waste liquid that is difficult to recycle and reuse; the chlorination step adopts the method of direct chlorine gas chlorination, which is easy to pollute the environment and is not conducive to labor protection; The cyclization step directly adopts solvent-free high-temperature cyclization, which produces a large amount of impurities, and the product purity is also not high

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