[Synthesis]
Example 43; This example illustrates the preparation of 6-methoxy-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)isoindolin-1-one in one embodiment of the present invention. Step A: Synthesis of 1-methyl-5-nitro-1H-pyrrolo[2,3-b]pyridine; 5-nitro-7-azaindole (0.195 g, 1.2 mmol) was dissolved in DMF (10 mL), NaH (60%, 0.057 g, 1.44 mmol) was added, followed by dropwise addition of iodomethane (0.204 g, 1.44 mmol). The reaction mixture was stirred at room temperature for 4.5 h. After completion of the reaction, the mixture was poured into water (200 mL) and extracted with dichloromethane (3 x 100 mL). The organic layers were combined, washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=50:50) to afford 1-methyl-5-nitro-1H-pyrrolo[2,3-b]pyridine (0.152 g, 72%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ9.23 (d, J=2.4Hz, 1H), 8.76 (d, J=2.4 Hz, 1H), 7.36 (d, J=3.6Hz, 1H), 6.66 (d, J=3.5Hz, 1H), 3.96 (s, 3H). |
[References]
[1] Patent: WO2009/42907, 2009, A1. Location in patent: Page/Page column 88
[2] Patent: WO2018/108704, 2018, A1. Location in patent: Page/Page column 72
[3] Patent: WO2018/171575, 2018, A1. Location in patent: Page/Page column 24; 33; 35; 73 |