Sodium Iodide → HCID 58368464, compound

Participants

Reaction Steps

A solution of 7-[(1S)-1-azidoethyl]-5-chloro-8-(3-fluorophenyl)cinnoline (48 g, 150 mmol) in methanol (430 mL) was treated with sodium iodide (130 g, 880 mmol) and stirred at room temperature for 10 minutes. The reaction mixture was cooled with a water bath. The reaction mixture was treated with chlorotrimethylsilane (110 mL, 880 mmol) dropwise over 20 minutes while maintaining the internal temperature at 28-35° C. The reaction mixture turned dark red and the stirring was continued for 26 min. After 42 min, the reaction mixture was treated with a solution of sodium sulfite (130 g, 1.0 mol) in water (430 mL). The dark red color of the solution faded and gave a yellow suspension. The reaction mixture was stirred for 30 minutes and then concentrated under reduced pressure to remove the methanol. The mixture was adjusted to pH>11 with 3 N NaOH solution and extracted with dichloromethane. The pH of the solution changed during the work-up, potentially due to the slow hydrolysis of TMSCl. The pH needed to be checked regularly and basified to pH>11 by addition of 3 N NaOH. The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the desired product (43 g, 96%) as a solid. LCMS for C16H14ClFN3 (M+H)+: m/z=302.1; Found: 302.0; 1H NMR (300 MHz, DMSO-d6): δ 9.47 (d, J=5.9 Hz, 1H), 8.41 (d, J=1.9 Hz, 1H), 8.29 (d, J=5.9 Hz, 1H), 7.59-7.49 (m, 1H), 7.34-7.14 (m, 3H), 4.04-3.95 (m, 1H), 2.22 (br s, 2H), 1.21-1.16 (m, 3H).

Provenance & Evidence