119043-16-2

Usage

Uses

Used in Pharmaceutical Industry:
4-2-[(3-Ethyl-2,5-dihydro-4-methyl-2-oxo-1H-pyrrol-1-yl)-carbonyl]-amino-ethyl-benzenesulfonyl chloride is used as an intermediate in the synthesis of 4-[2-[(3-Ethyl-4-methyl-2-oxo-3-pyrrolin-1-yl)carboxamido]ethyl]benzenesulfonamide (E925045). 4-2-[(3-Ethyl-2,5-dihydro-4-methyl-2-oxo-1H-pyrrol-1-yl)-carbonyl]-amino-ethyl-benzenesulfonyl chloride is further utilized in the preparation of Glimepiride, a sulfonylurea hypoglycemic agent used as an antidiabetic medication. The synthesis of these compounds is crucial for the development of effective treatments for diabetes and related conditions.

InChI:InChI=1/C16H19ClN2O4S/c1-3-14-11(2)10-19(15(14)20)16(21)18-9-8-12-4-6-13(7-5-12)24(17,22)23/h4-7H,3,8-10H2,1-2H3,(H,18,21)

Upstream product

• 1943-82-4 phenethyl isocyanate 
• 247098-18-6 3-ethyl-4-methyl-2-oxo-N-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 607-97-6 ethyl 2-ethyl-3-oxobutanoate 
• 247098-17-5 ethyl-α-ethylacetoacetate cyanohydrin 
• 766-36-9 3-ethyl-4-methyl-3-pyrrolin-2-one 

Downstream Products

• 119018-29-0 N-{2-[4-(aminosulfonyl)phenyl]ethyl}-3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 599174-28-4 C₃₂H₄₂N₄O₇S 

Relevant academic research and scientific papers

Glimepiride impurity and preparation method thereof

The invention provides a glimepiride impurity and a preparation method thereof. The chemical name of the impurity is ethyl 4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrrolin-1-formylamino)ethyl]benzenesulfonate. The preparation method comprises the following steps: A, reacting 3-ethyl-4-methyl-2-oxo-N-phenethyl-2, 5-dihydro-1H-pyrrol-1-amide with chlorosulfonic acid to obtain 1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrrolin-1-formamido)-ethyl]-benzenesulfonyl chloride; B, reacting the 1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrrolin-1-formamido)-ethyl]-benzenesulfonyl chloride with an ethanol solution of sodium ethoxide to obtain an impurity crude product; and C, adding the impurity crude product into a mixed solution of methyl isobutyl ketone and acetone for purification, and separating to obtain the impurity. The purity of the prepared impurity can reach 99.5% or above, and the impurity can be used as an impurity reference substance for glimepiride bulk drug or preparation quality control.

Preparation method of high-purity glimepiride

The invention discloses a preparation method of high-purity glimepiride. The preparation method comprises the following specific steps: 1, adding 1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)-ethyl]-benzenesulfonamide and potassium carbonate into a mixed solvent, and raising the temperature to dissolve the added substances; and 2, carrying out cooling crystallization on a solution obtained in step 1, and filtering the cooled solution to obtain 1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)-ethyl]-benzenesulfonyl]-3-(trans-4-methylcyclohexyl)-urea. The glimepiride obtained by the preparation method has a purity of above 99.9% and a high yield, impurity research is sufficient and controllable, the crystal form is correct, and the preparation product quality is good,so the use requirements of people are met.

Preparation method of glimepiride intermediate

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.

Process for synthesizing glimepiride raw material medicine

The invention discloses a process for synthesizing a glimepiride raw material medicine. A compound A, namely 3-ethyl-4-methyl-3-pyrroline-2-ketone and a compound B, namely 2-phenethyl isocyanate are taken as start raw materials. The process is characterized in that when an intermediate 1 is synthesized, filtrate is applied mechanically, so that the loss of the intermediate 1 can be reduced, the yield can be increased, and the production efficiency can be improved; when an intermediate 2 is synthesized, hydrochloric ether is adopted as a solvent, so that isomer impurities can be greatly reduced, the content of the isomer impurities can be reduced to 0.5% or less from 8%, and later purification procedures can be simple to operate; when a glimepiride metallic salt is synthesized, acetonitrileis adopted as a solvent, sufficient reactions can be achieved, the reaction time can be greatly shortened, the residue of an intermediate 3 is reduced to 0.2% or less from 5-10%, in addition, a highsolvent recycling rate can be achieved. The process disclosed by the invention is simple and safe, low in production cost, high in yield, stable in intermediate and finished product quality and applicable to industrial large-scale production and hypoglycemic drug, namely glimepiride, synthesis processes with relatively great social, economic and environmental-friendly benefits.

A NOVEL PROCESS FOR PREPARATION OF SUBSTANTIALLY PURE GLIMEPIRIDE

The present invention discloses a novel process for purification of trans-4-methyl cyclohexylamine HC1 and 4-[2-(3-Ethyl-4-methyl-2-carbonyl pyrrolidine amido) ethyl] benzene sulfonamide used in the synthesis of 3-Ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(trans-4-methyl cyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide(I), popularly known as Glimepiride. The present invention also discloses a novel purification of Glimepiride Form I (I), having the undesired cis isomer below 0.15%. Glimepiride (I) is useful in the treatment of diabetes mellitus.

Total synthesis of cis and trans-hydroxyglimepiride: Active metabolite of glimepiride

Syntheses of trans-hydroxyglimepiride 2b, a human metabolite of the blood glucose lowering agent glimepiride 1 and its corresponding cis-stereoisomer 2a, are described.