Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of glimepiride intermediate

A technology for intermediates and compounds, applied in the field of API preparation, can solve the problems of impurities Ⅴ and Ⅵ exceeding the standard and exceeding the limit, difficult to remove, and low impurity content.

Active Publication Date: 2019-08-06
迪嘉药业集团股份有限公司
View PDF8 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Purpose of the invention: To solve the problem that the compound I prepared by the prior art has high impurity content and is difficult to remove, to provide a method for preparing compound I with low impurity content
[0020] Because the purification of 4-(2-aminoethyl)benzenesulfonamide is relatively easy, it is easy to obtain high-purity commercial raw materials, and according to the method of route 2 document (3), the problem of exceeding the standard and exceeding the limit of impurities Ⅴ and Ⅵ is solved question

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of glimepiride intermediate
  • Preparation method of glimepiride intermediate
  • Preparation method of glimepiride intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1（1

[0047] Embodiment 1 (the acetic acid of 1.0 molar equivalent)

[0048]Compound IX 5.0g, 4-(2-aminoethyl)benzenesulfonamide 4.08g, acetic acid 1.22g and isopropanol 50g were heated to reflux for 8h (the remaining amount of 4-(2-aminoethyl)benzenesulfonamide was 0.74% ), cooled at 25°C, filtered, and dried at 50°C to obtain 6.67g of compound Ⅰ, with a purity of 99.86% by HPLC, 0.05% of impurity Ⅷ, no impurities Ⅴ and Ⅵ, and a yield of 93.2%

Embodiment 2（1

[0049] Embodiment 2 (1.0 molar equivalent of acetic acid amplification effect)

[0050] 40.0g of compound VIII, 32.64g of 4-(2-aminoethyl)benzenesulfonamide, 9.8g of acetic acid and 160g of isopropanol were heated to reflux for 8h, cooled at 25°C, filtered, and dried at 50°C to obtain 53.65g of compound Ⅰ, yield 93.6%, HPLC detection purity 99.78%, impurity Ⅷ 0.06%, impurity Ⅴ and Ⅵ not detected.

Embodiment 3（2

[0051] Embodiment 3 (acetic acid of 2.0 molar equivalents)

[0052] Compound Ⅷ 10.0g, 4-(2-aminoethyl)benzenesulfonamide 8.16g, glacial acetic acid 4.9g and isopropanol 50g were heated to reflux for 7h, cooled at 25°C, filtered and dried at 50°C to obtain 13.18g of compound Ⅰ. The rate was 92.0%, the purity by HPLC was 99.71%, the impurity VIII was 0.04%, and the impurities V and VI were not detected.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a preparation method of a glimepiride intermediate compound I, and belongs to the technical field of preparation of raw material medicines. The preparation method comprises the following steps: reacting a compound II with diphenyl carbonate under the catalysis of an alkali (referring to Synlett, 28(18), 2495-2498; 2017) to prepare a compound IX; and adding a compound IX and 4-(2-aminoethyl)benzenesulfonamide according to a ratio of 1:1, adding a weak acid, adding isopropanol, and performing heating for a refluxing reaction. The invention provides the preparation methodof the glimepiride intermediate with a high purity.

Description

technical field [0001] The invention relates to a preparation method of glimepiride intermediate compound I, which belongs to the technical field of preparation of raw materials. Background technique [0002] Glimepiride is a third-generation sulfonylurea long-acting antidiabetic drug developed by the German company Hoechst in the 1980s. It was first launched in Sweden under the trade name Amaryl in September 1995. Since glimepiride has a weak effect on cardiovascular KATP channels, there are few adverse cardiovascular reactions. Glimepiride has the advantages of high efficiency, long-term effect, less dosage (2~4mg / d), and less side effects. [0003] All current synthetic routes to glimepiride require the use of the intermediate 4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)ethyl] Benzenesulfonamide (i.e. compound I). [0004] . [0005] At present, the synthesis literature reports about this intermediate mainly contain the following two routes: [0006] rou...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D207/38
CPCC07D207/38Y02P20/55
Inventor 吴荣贵薛复照徐可岭王常德
Owner 迪嘉药业集团股份有限公司