1-Methylindole-2-carboxylic acid

Chemical Properties

Beige crystalline powder

Uses

• Reactant for preparation of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
• Reactant for synthesis of fenbufen and ethacrynic acid derivatives as potential antitumor agents via amide coupling reactions
• Reactant for diastereoselective synthesis of vinylated heterocycles via ruthenium-catalyzed oxidative vinylation with alkenes
• Reactant for synthesis of 2,3-dihalo indoles via hypervalent iodine mediated decarboxylative halogenation
• Reactant for preparation of α-ketoamides as cathepsin S inhibitors with potential applications against tumor invasion and angiogenesis
• Reactant for preparation of anthranilic acid mimics as bacterial translation inhibitors

Uses

• ;Reactant for preparation of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors1• ;Reactant for synthesis of fenbufen and ethacrynic acid derivatives as potential antitumor agents via amide coupling reactions2• ;Reactant for diastereoselective synthesis of vinylated heterocycles via ruthenium-catalyzed oxidative vinylation with alkenes3• ;Reactant for synthesis of 2,3-dihalo indoles via hypervalent iodine mediated decarboxylative halogenation4• ;Reactant for preparation of α-ketoamides as cathepsin S inhibitors with potential applications ag

General Description

1-Methylindole-2-carboxylic acid reacts with thionyl chloride to yield sulfinyl chlorides.

Synthesis

The general procedure for the synthesis of 1-methylindole-2-carboxylic acid from methyl 1-methyl-1H-indole-2-carboxylate was as follows: to a mixed solution of THF/H2O (2:1, 15 mL) of methyl 1-methyl-1H-indole-2-carboxylate (250 mg, 1.32 mmol) at 23 °C, LiOH-H2O (291 mg, 6.94 mmol). The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the mixture was concentrated under reduced pressure to remove the solvent and subsequently partitioned between H2O (100 mL) and ether (100 mL). The aqueous layer was adjusted to pH 2-3 with 1.0 N HCl and then extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, dried over anhydrous MgSO4, filtered and concentrated to give 1-methyl-1H-indole-2-carboxylic acid (210 mg, 91% yield).

References

[1] Tetrahedron, 2004, vol. 60, # 44, p. 10039 - 10047
[2] Journal of Organic Chemistry, 2016, vol. 81, # 16, p. 7288 - 7300
[3] Advanced Synthesis and Catalysis, 2018, vol. 360, # 11, p. 2093 - 2100
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5298 - 5310
[5] Patent: US2006/211603, 2006, A1. Location in patent: Page/Page column 71