Diisopropylethylamine → Ethyl5-chloro-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

Participants

Reaction Steps

To a slurry of 5-chloro-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyridine-6-carboxylic acid (0.46 g, 1.623, 1 equiv) and 1-(cyanomethyl)tetrahydro-1H-thiophen-1-ium, bromide salt (0.47 g, 2.27 mmol, 1.4 equiv) in DCM (16 mL) was added DIPEA (1.13 mL, 6.49 mmol, 4 equiv) then HATU (0.86 g, 2.27 mmol, 1.4 equiv). After 2 h, more 1-(cyanomethyl)tetrahydro-1H-thiophen-1-ium, bromide salt (0.20 g) and DIPEA (0.5 mL) added. After stirring 18 h, the reaction was added to saturated aqueous NaHCO3 and extracted with DCM (×2). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The crude sulfur ylide was taken up in MeOH (16 mL) and a solution of Oxone (2.4 g, 3.90 mmol, 2.4 equiv) in water (5 mL) was added. After 2 d, more Oxone (2.4 g, 3.90 mmol, 2.4 equiv) was added. After 6 h, the reaction was added cautiously to saturated aqueous NaHCO3 and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (20-100% EtOAc/hex) to provide the product (0.40, 76%) as a viscous yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.37 (d, J=0.8 Hz, 1H), 7.55-7.52 (m, 1H), 4.51 (q, J=7.2 Hz, 2H), 4.01 (s, 3H), 2.40 (d, J=1.1 Hz, 3H), 1.47 (t, J=7.2 Hz, 3H); LCMS (ESI, M+1): 325.05.

Provenance & Evidence