Uses
7-Ethyl-1H-indole-2,3-dione is used in the synthetic preparation of substituted indolin-2-ones as p90 ribosomal s6 protein kinase 2 (RSK2) inhibitors.
Synthesis
Intermediate 62 was ground as described by Yang et al. (see J. Am. Chem. Soc., 1996, 118:9557) and added in portions to a 50 mL conical flask containing 15 mL of concentrated sulfuric acid while maintaining stirring and maintaining the temperature at 90°C. Acetamide was added slowly, ensuring that the temperature of the reaction mixture did not exceed 105 °C. After addition, the purple-black solution was continued to be stirred at 90°C for 15 minutes, subsequently cooled to 60°C and poured into a beaker containing 15 g of crushed ice. Ice was continued to be added until the outside of the beaker was cold to the touch. The orange-brown precipitate was collected by filtration and dried overnight under vacuum to afford dihydroindole-2,3-dione (Intermediate 63, 0.77 g, 27% yield) of sufficient purity for use in the next step. Intermediate 63 was also recrystallized from ethanol to give a pure orange-red needle product.1H NMR (400 MHz, DMSO-d6) δ 1.14 (t, J = 7.5 Hz, 3H), 2.56 (q, J = 7.6 Hz, 2H), 7.03 (t, J = 7.5 Hz, 1H), 7.35 (d, J = 7.3 Hz, 1H), 7.46 (d , J = 7.6 Hz, 1H), 11.11 (s, 1H).
References
[1] Bulletin of the Chemical Society of Japan, 2006, vol. 79, # 10, p. 1585 - 1600
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 3, p. 628 - 630
[3] Patent: US2008/255192, 2008, A1. Location in patent: Page/Page column 22-23
[4] Journal of Medicinal Chemistry, 2010, vol. 53, # 16, p. 6003 - 6017
[5] Journal of Organic Chemistry, 2018, vol. 83, # 15, p. 7622 - 7632
