5-Methoxyindole-2-carboxylic acid

Chemical Properties

LIGHT YELLOW TO BROWNISH POWDER

Uses

Reactant for preparation of:• ;Anticancer agents1• ;A fluorescent small molecule probe for in vivo lipid imaging2• ;Indoleamine 2,3-dioxygenase (IDO) inhibitors3• ;Selective Dopamine D3 receptor ligands4• ;5-HT4 receptor ligands5• ;Inhibitors of Mycobacterium tuberculosis pantothenate synthetase6• ;Hypoxia selective cytotoxins7• ;Potent antitumor bifunctional DNA alkylating agents8

Uses

5-Methoxyindole-2-carboxylic Acid is a very useful synthetic intermediate. It is a reactant used to prepare anticancer agents, Indoleamine 2,3-dioxygenase (IDO) inhibitors, and potent antitumor bifunctional DNA alkylating agents.

Uses

Reactant for preparation of:

• Anticancer agents
• A fluorescent small molecule probe for in vivo lipid imaging
• Indoleamine 2,3-dioxygenase (IDO) inhibitors
• Selective Dopamine D3 receptor ligands
• 5-HT4 receptor ligands
• Inhibitors of Mycobacterium tuberculosis pantothenate synthetase
• Hypoxia selective cytotoxins
• Potent antitumor bifunctional DNA alkylating agents

Definition

ChEBI: 5-methoxyindole-2-carboxylic acid is an indolecarboxylic acid that is indole-2-carboxylic acid carrying an additional methoxy substituent at position 5. It has a role as a plant metabolite, a hypoglycemic agent and an EC 1.8.1.4 (dihydrolipoyl dehydrogenase) inhibitor. It is an indolecarboxylic acid and an aromatic ether.

Synthesis

124-38-9

169383-96-4

4382-54-1

To a solution of 2-bromo-5-methoxy-1H-indole (1.0 g, 4.4 mmol, 1.0 eq.) in anhydrous THF (20 mL) was slowly added 2M isopropylmagnesium chloride (i-PrMgCl) in THF solution (2.2 mL, 4.4 mmol, 1.0 eq.) at 0 °C. The reaction mixture was stirred at this temperature for 5 minutes, followed by the dropwise addition of 2.5 M hexane solution (3.5 mL, 8.8 mmol, 2.0 eq.) of n-butyllithium (n-BuLi) over a period of 5 minutes, controlling the reaction temperature to not exceed 20 °C. The resulting mixture was continued to be stirred at 0 °C for 30 min and then passed through dry carbon dioxide gas (0.20 g, 4.4 mmol, 1.0 eq.). The reaction system was slowly warmed to 20 °C over 0.5 h and the reaction was quenched with deionized water (6 mL). After stirring for 10 min, the organic and aqueous phases were separated and the aqueous phase was extracted once with ethyl acetate (10 mL). The organic phases were combined, the suspension was returned to room temperature, filtered through a silica gel pad (0.5 cm) and eluted with ethyl acetate (10 mL). The filtrate was concentrated and the residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 3:1) to afford the brown solid product 5-methoxyindole-2-carboxylic acid (0.68 g, 80% yield) with a melting point of 199-201 °C. The structure of the product was confirmed by 1H-NMR (600 MHz, DMSO-d6) and 13C-NMR (151 MHz, DMSO-d6).

References

[1] Molecules, 2017, vol. 22, # 11,