20780-74-9

7-bromoisatin was treated with excess PhMgBr to afford tertiary alcohol 9 in 96 % yield. Isatin oxime triflates undergo a facile fragmentation which is promoted by DBU, to form anthranilonitriles after hydrolytic work-up.

Step 2: N-(2-bromophenyl)-2-(hydroxyimino)acetamide (7 g, 0.028 mol) was slowly added to 70 mL of concentrated sulfuric acid, and the temperature of the reaction system was maintained at 60 °C. Subsequently, the reaction temperature was raised to 90 °C with continuous stirring for 3 hours. Upon completion of the reaction, the reaction mixture was slowly poured into ice water and a yellow precipitate was precipitated. The precipitate was collected by filtration and dried to give 7-bromoisatin as a yellow solid (6.0 g, 92% yield). The product was characterized by 1H NMR (300 MHz, DMSO-d6): δ 11.33 (s, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.52 (d, J = 7.2 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H); LC-MS (ESI) analysis: calculated mass: 224.9; observed mass: 226.0 [M + H]+ (retention time: 0.39 min).

[1] Patent: WO2012/58671, 2012, A1. Location in patent: Page/Page column 106
[2] Patent: CN105732462, 2016, A. Location in patent: Paragraph 0026
[3] Patent: CN103864779, 2016, B. Location in patent: Paragraph 0066; 0067; 0069
[4] Patent: WO2011/119704, 2011, A1. Location in patent: Page/Page column 38
[5] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 1, p. 22 - 26