Application
6-Methoxyindigo is an important pharmaceutical and chemical intermediate that can be used as a starting material in the synthesis of various natural products and active compounds. For example, it can be used to synthesize the spirohydroxyindole alkaloid strychnofoline, which exhibits good antitumor activity. A derivative of 6-methoxyindigo, NMP6, can be used as a fluorescent probe for the CB2 receptor, enabling visualization of receptor binding on immune cells.
Synthesis
2-Hydroxyimino-N-(3-methoxyphenyl)-acetamide (Compound 15, 3.0 g, 15.46 mmol) was added to polyphosphoric acid (30.0 g) and the reaction was stirred at 55 °C for 1 hour. After completion of the reaction, ice water was added to quench the reaction under cooling in an ice bath. The reaction mixture was extracted with ethyl acetate, and the organic phase was sequentially washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The organic phase was concentrated under reduced pressure to afford 6-methoxydihydroindole-2,3-dione (compound 16) as a red solid (2.2 g, 82% yield).
References
[1] Synthetic Communications, 1994, vol. 24, # 4, p. 533 - 548
[2] Patent: JP2017/81888, 2017, A. Location in patent: Paragraph 0053; 0055
[3] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 21, p. 3261 - 3273
[4] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 2, p. 125 - 128
[5] Patent: WO2009/14730, 2009, A1. Location in patent: Page/Page column 158
