197776-07-1

Usage

Uses

Used in Pharmaceutical Industry:
5-chloro-1-ethoxycarbonyl-2-oxo-2,3-dihydroindole is used as an intermediate for the synthesis of 2-Cyclobutenyl-3-trifluoromethyl-5-chloro-1H-indole-1-carboxylic Acid Ethyl Ester. 5-chloro-1-ethoxycarbonyl-2-oxo-2,3-dihydroindole is further utilized in the preparation of novel GSK-3β inhibitors, which are potential anticancer agents. The development of these inhibitors is significant for their potential role in targeting and treating various types of cancer.

Upstream product

• 17630-75-0 5-chloro-indolin-2-one 
• 541-41-3 chloroformic acid ethyl ester 
• 197775-85-2 5-chloro-1-ethoxycarbonyl-2-(ethoxycarbonyloxy)indole 

Downstream Products

• 301700-20-9 2-benzyloxycarbonyloxy-5-chloro-indole-1-carboxylic acid ethyl ester 
• 301700-21-0 5-chloro-2-phenoxycarbonyloxy-indole-1-carboxylic acid ethyl ester 
• 1309883-52-0 ethyl (2R,6R)-5'-chloro-2',4-dioxo-2,6-diphenylspiro[cyclohexane-1,3'-indoline]-1'-carboxylate 

Relevant academic research and scientific papers

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P1 agonist precursor developed by Merck.

New practical synthesis of tenidap

The development of a new, practical synthesis to tenidap is described. N,O-Dialkoxy(aryloxy)carbonylation of 5-chloro-2-oxo-2,3-dihydroindole, followed by removal of the O-alkoxy-(aryloxy)carbonyl group gave 1-[alkoxy(aryloxy)carbonyl]-5-chloro-2-oxo-2,3-dihydroindoles in good yields. The latter compounds were thenoylated in the 3-position. The role of DMAP in the acylation reaction is discussed. The structures of the thenoylated products and their enolate salts were investigated both in solution and solid phases. Ammonolysis of 5-chloro-3-[1-hydroxy-1-(2-thienyl)methylene]-2-oxo-1-phenoxycarbonyl-2,3- dihydroindole afforded the corresponding 1-carbamoyl derivative (tenidap) in high yield. The corresponding 1-ethoxy- and 1-methoxycarbonyl derivatives could not be similarly transformed to tenidap; loss of the alkoxycarbonyl moiety occurred instead of carbamoylation.

Synthesis of 1,3-di[alkoxy(aryloxy)carbonyl]-2-oxo-2,3-dihydroindoles

Two protocols have been developed for the synthesis of 1,3-di[alkoxy(aryloxy)carbonyl]-2-oxo-2,3-dihydroindoles starting from the corresponding N,O-diacyl derivatives obtained by treatment of 2-oxindoles with chloroformic acid esters and triethylamine. Th