Chemical Properties
light brown to grey crystalline powder
Uses
4-Methoxyindole is a reactant for alpha-ethyltryptamines as dual dopamine-serotonin releasers.
Application
Reactant for preparation of:
GABA analogs
Sodium-Dependent Glucose Co-transporter 2 (SGLT2) Inhibitors for the Management of Hyperglycemia in Diabetes
Anticancer agents
Integrase strand-transfer inhibitors (INSTIs)
Inhibitor of Proliferation of Colon Cancer Cells
Isomeridianin G as GSK-3? inhibitors
HIV-1 integrase inhibitors
Inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)
4-Methoxyindole was used for comparing the complexation reaction of β-cyclodextrin (β-CD) with pindolol using reversed-phase liquid chromatography.
Biotechnological Applications
4-Methoxyindole is used in a variety of preparation procedures. It is a reactant involved in the synthesis of GABA analogs, HIV-1 integrase inhibitors, anticancer agents, sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors, integrase strand-transfer inhibitors (INSTIs), and isomeridianin G. Additionally, it is used in reverse-phase liquid chromatography analysis of the reaction of β-cyclodextrin and pindolol.
Synthesis
Step1 :1-[(E)-2-(2-methoxy-6-nitrophenyl)vinyl]pyrrolidine: To a solution of 10 g of 1-methoxy-2-methy3-nitrobenzene in 100 ml of DMF are added 8.74 ml of N,N-dimethylformamide dimethyl acetal and 5.44 ml of pyrrolidine, and the mixture is then refluxed for 3 hours. The mixture is concentrated to half its volume under vacuum, the remaining mixture is poured into ether/water and extracted with ether, the organic phase is washed with saturated NaCl solution and dried over MgSO4 , and the solvent is evaporated off under vacuum. 1-[(E)-2-(2-methoxy-6-nitrophenyl)vinyl]pyrrolidine; yield 14.6 g.
Stpe 2 : synthesis of 4-Methoxyindole, A suspension of 150 ml of zinc powder in 500 ml of 0.5N HCl is stirred for 1 hour at room temperature. The suspension is ded by suction, washed with water to neutral pH, with anhydrous EtOH and then with ether, and dried. To a solution of 10 g of the compound from the preceding step in 46 ml of acetic acid are added, portionwise, 31.6 g of activated zinc, while keeping the temperature between 20 and 30°C using an ice bath. The reaction mixture is stirred at room temperature for 30 minutes, and is filtered. The filtrate is extracted with EtOAc, the organic phase is washed with NaHCO3 solution and with saturated NaCl solution, and dried over MgSO4 , and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with a cyclohexane/EtOAc mixture in a gradient of from (98/2 v/v) to (95/5 v/v). 4-Methoxy- 1H-indole; yield 1.6 g.
