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Method for synthesizing gliclazide and intermediate thereof

A synthesis method and compound technology, applied in the preparation of sulfonamides, organic chemistry, etc., can solve problems such as difficult control of reaction conditions, and achieve the effects of being easily oxidized, reducing impurities, and improving product quality

Active Publication Date: 2012-09-05
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The disadvantages of this reaction process are: the reaction conditions are difficult to control, and the ring expansion reaction is prone to generate six-membered ring by-products

Method used

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  • Method for synthesizing gliclazide and intermediate thereof
  • Method for synthesizing gliclazide and intermediate thereof
  • Method for synthesizing gliclazide and intermediate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Add 30g of p-toluenesulfonylurea (compound V), 19.5g of sodium carbonate, 200ml of n-butanol, and 11g of hydrazine hydrate into a 500ml reaction flask. 300ml of water, separated to remove the organic layer, the aqueous layer was adjusted to PH=7 with hydrochloric acid, a large amount of white solids precipitated, filtered with suction, washed with water, and the warm product was dried at 65-70°C for 12 hours to obtain 23g of the target product N-[(4-methylbenzene base) sulfonyl]-hydrazide carboxamide (compound IV), yield 71.6%.

Embodiment 2

[0034] Add p-toluenesulfonylurea (compound V) 30g, sodium carbonate 19.5g, n-butanol 200ml, hydrazine hydrate 11g in the 500ml reaction bottle, add, heat to reflux, keep warm for 12 hours, keep warm, and recover normal by vacuum distillation. After 150ml of butanol, add 300ml of water, distill 50ml under normal pressure, cool to room temperature, adjust PH=7 with hydrochloric acid, a large amount of white solid precipitates, filter with suction, wash with water, and dry the warm product at 65-70°C for 12 hours to obtain 30g of the target product N- [(4-Methylphenyl)sulfonyl]-hydrazide carboxamide (compound IV), yield 93.4%.

Embodiment 3

[0035] Example 3: Synthesis of 1-(1,3-dicarbonyl-hexahydrocyclopentadieno[c]pyrrol-2(1H)-yl)-3-p-toluenesulfonylurea (Compound II)

[0036] Add 3.0g p-toluenesulfonic acid, N-[(4-methylphenyl)sulfonyl]-hydrazide carboxamide (compound IV) 19.5g, 1,2-cyclopentane phthalic anhydride in a 500ml reaction flask (Compound III) 15g, toluene 200ml, after adding, heat to reflux, reflux and divide water for 12 hours, divide water, add 300ml water after decompression distillation reclaims 150ml toluene, normal pressure distillation reclaims 100ml of hydrated toluene, cool to room temperature, Suction filtration, washing with water, drying the warm product at 65-70°C for 12 hours to obtain 18 g of the target product 1-(1,3-dicarbonyl-hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3- p-toluenesulfonylurea (compound II), yield 60.2%.

[0037] p-toluenesulfonic acid acts as an acid catalyst in this reaction.

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Abstract

The invention relates to a method for synthesizing gliclazide and an intermediate thereof, which comprises the following steps of: performing a condensation reaction of p-toluenesulfonylurea serving as a raw material and hydrazine hydrate to obtain a compound IV; reacting the compound IV with 1,2-cyclopentanedicarboxylic anhydride to obtain a compound II; and finally performing a reduction reaction of the compound II to obtain the gliclazide, wherein the compound II is a new intermediate compound. The gliclazide is synthesized by the method, amino heterocycles are not used, and the problem ofoxidizing the raw material easily is solved fundamentally.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to a synthesis method of gliclazide and its intermediates. Background technique [0002] Gliclazide, English name: Gliclazide, molecular formula: C 15 h 21 N 3 o 3 S, CAS number: 21187-98-4, its chemical name is 1-(hexahydrocyclopenta[c]pyrrol-2(IH)-yl)-3-(4-methylphenyl-)sulfonylurea ( 1-(hexahgdroeycloxpenta[c]pyrrol-2(IH)-yl)-3-[(4-methylphangl)sulphonyl]urea)), the chemical structure is shown in formula I: [0003] [0004] It is a second-generation sulfonylurea oral hypoglycemic agent, mainly used for the treatment of type II (non-insulin-dependent) diabetes. The occurrence of complications has been widely used clinically. [0005] The report on Gliclazide first appeared in the US patent US 3501495 (patent owner: SCIENCE UNION & CIE). This patent was published as early as March 17, 1970, and the disclosed process route is as follows: [0006] [0007] The problem w...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/52C07C311/61C07C303/40
CPCC07D209/52
Inventor 车大庆杜小华
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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