Dimethylformamide → 8-Chloro-3-(methylsulfanyl)imidazo[1,5-A]pyrazine

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Reaction Steps

To a solution of (3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester (3.05 g, 0.0140 mol) in MeCN (70 mL) were added DMF (4.3 mL, 0.056 mol) and POCl3 (5.2 mL, 0.056 mol) at 0° C. under nitrogen. The reaction mixture was slowly warmed to rt and stirred at rt overnight. LC-MS showed the SM was completely consumed. The solvent was evaporated under reduced pressure and the residue was cooled at 0° C. and diluted with EtOAc (250 mL), then quenched with sat. aq. NaHCO3 (100 mL). The mixture was washed brine (50 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hexane EtOAc=80:20→70:30) to give the title compound as a light-yellow solid, 1.75 g, 63% yield. LC-MS (ES+): 200/202 (3/1) [MH+], and 1H NMR (CDCl3, 400 MHz): δ 2.71 (s, 3H), 7.40 (d, J=5.1 Hz, 1H), 7.74 (dd, J=5.1, 1.0 Hz, 1H), 7.90 (s, 1H).

Provenance & Evidence