745052-94-2

Usage

Uses

Used in Organic Synthesis:
Ethyl 2-(4-(cyclopropylthio)phenyl)-2-oxoacetate is used as a chemical reagent for various chemical reactions in the field of organic synthesis. Its unique structure allows it to participate in a range of reactions, making it a valuable component in the synthesis of more complex organic molecules.

InChI:InChI=1/C13H14O3S/c1-2-16-13(15)12(14)9-3-5-10(6-4-9)17-11-7-8-11/h3-6,11H,2,7-8H2,1H3

Upstream product

• 14633-54-6 cyclopropylphenylsulfide 
• 108-98-5 thiophenol 
• 4755-77-5 Ethyl oxalyl chloride 

Downstream Products

• 876063-40-0 (4-cyclopropylsulfonylphenyl)-2-oxo-acetic acid ethyl ester 
• 1058167-41-1 ethyl 2-[4-(cyclopropylthio)phenyl]-3-[(1α,3α,4α)-3,4-difluorocyclopentyl]acrylate 
• 1397795-19-5 (E)-ethyl 2-(4-(cyclopropylthio)phenyl)-3-(tetrahydro-2H-pyran-4-yl)acrylate 
• 1397795-26-4 (Z)-ethyl 2-(4-(cyclopropylthio)phenyl)-3-(tetrahydro-2H-pyran-4-yl)acrylate 
• 1080059-87-5 methyl 2-(4-cyclopropylsulfonylphenyl)acetate 
• 1143510-49-9 2-(4-cyclopropanesulfonylphenyl)-2-(2,4-difluorophenoxy)acetic acid 
• 1328985-59-6 4-{2-[2-(4-cyclopropanesulfonylphenyl)-2-(2,4-difluorophenoxy)acetylamino]thiazol-5-yloxy}benzoic acid 
• 1328983-37-4 methyl 4-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]oxybenzoate 
• 1328984-60-6 methyl 3-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]oxybenzoate 
• 1328984-99-1 methyl 2-[4-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]oxyphenyl]acetate 
• 1328994-82-6 3-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]oxybenzoic acid 
• 1328995-50-1 2-[4-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]oxyphenyl]acetic acid 
• 1328995-70-5 4-[[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]methyl]benzoic acid 
• 1328995-86-3 1-[[2-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]thiazol-5-yl]methyl]piperidine-4-carboxylic acid 

Relevant academic research and scientific papers

Practical and Scalable Synthesis of a Glucokinase Activator via One-Pot Difluorination and Julia Olefination

We describe the process research and development of a practical synthesis of glucokinase activator 1 as a potential drug for treating type 2 diabetes mellitus. The key structure, a 3,4-cis-difluorinated cyclopentane moiety, was constructed via diastereoselective epoxidation, followed by one-pot difluorination with Et3N·3HF and perfluorobutanesulfonyl fluoride (PBSF). Julia olefination of benzothiazol-2-yl sulfone with glyoxylate furnished an E/Z mixture of acrylate, followed by isomerization of the alkene to the desired E configuration during the formation of the acid chloride in the final step. This development achieved a highly practical process route to 1 (15percent overall yield, 12 steps). This process route overcomes the drawbacks of the original medicinal chemistry synthetic route, which used hazardous and costly reagents (LiAlH4, OsO4, and Deoxo-Fluor) and had low efficiency (4percent overall yield, 20 steps).

Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia

Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite effective blood glucose lowering in clinical trials, many pan-GKAs “acting both in pancreas and liver” have been discontinued from cli

Scalable synthesis of a nonracemic α-arylpropionic acid via ketene desymmetrization for a glucokinase activator

Process research and development for a synthesis of the chiral carboxylic acid (R)-2 as a key intermediate of the glucokinase activator (R)-1 is described. The construction of the stereocenter at the α-carbon is a key point for the synthesis of (R)-2. The proposed process utilizes desymmetrization of a ketene in situ generated from the corresponding racemic carboxylic acid Rac-2 with (R)-pantolactone as a chiral auxiliary followed by hydrolysis of the resulting ester. This key step has been successfully scaled up to 20 kg, which demonstrates that this synthetic approach is comparable with a previously reported approach via enantioselective hydrogenation.

Acetamide compounds as glucokinase activators, their process and medicinal applications

Acetamide derivatives, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof for the prophylaxis, management, treatment, control of progression, or adjunct treatment of diseases and/or m

Development of an enantioselective hydrogenation based synthesis of a glucokinase activator

This article describes the development and optimization of chemical reactions and subsequent multikilogram preparation of the glucokinase activator (R)-1 to fund clinical evaluation as a potential therapeutic for type II diabetes. The major process developments presented here are a Wittig olefination isomerization based synthesis of an E-acrylic acid, an optimized enantioselective hydrogenation of the E-acrylic acid, and a challenging final amide coupling.

ACETAMIDE COMPOUNDS, THEIR PROCESS AND PHARMACEUTICAL APPLICATION

This disclosure relates to a series of acetamide compounds of formula (I), their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof. The disclosure also relates to process of preparation of

ACETAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATORS, THEIR PROCESS AND MEDICINAL APPLICATION

Acetamide derivatives, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof for the prophylaxis, management, treatment, control of progression, or adjunct treatment of diseases and/or m

CRYSTALLINE (R)-2-(4-CYCLOPROPANESULPHONYL-PHENYL)-N-PYRAZIN-2-YL-3-(TETRAHYDROPYRAN-4-YL)-PROPIONAMIDE

Crystalline R-2-(4-cyclopropanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydropyran-4-yl)-propionamide and methods of its preparation and use are disclosed.

NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME

Compounds are provided which are glucokinase activators and thus are useful in treating diabetes and related diseases and have the structure wherein in the ring represents one or two double bonds; R1 is aryl or heteroaryl; R2 is halogen, cycloalkyl, heterocyclyl, aryl, or heteroaryl; R5 is as defined herein; Z is O, S, S(O), S(O)2, or NR5a; X is S, O, N, NR3, or CR3; Y is NCR4 or N4; R3, R4, and R5 are as defined herein; R8 is aryl or heteroaryl; R6 and R7 are independently H, halogen, or alkyl; m is 0 or 1; and n is 0 to 3, or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME

Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n-Z-(CH2)m—PO(OR7)(OR8), —(CH2)nZ-(CH2)m—PO(OR7)Rg, —(CH2)n-Z-(CH2)m—OPO(OR7)Rg, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10);R5 and R6 are independently selected from H, alkyl and halogen;Y is R7(CH2)s or is absent; andX, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.