Dichloromethane → 2-(3,4-Dimethoxyphenyl)-5-(5-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazole

Participants

Reaction Conditions

Reaction Steps

2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.20 g, 0.606 mmol, 1 eq) was dissolved in dioxane (4 mL), and 3,4-dimethoxyphenylboronic acid was added (0.121 g, 0.667 mmol, 1.1 eq) followed by a saturated solution of K2CO3 (1 mL). The suspension was degassed (N2, 10 min), and Pd(dppf)Cl2.DCM (0.085 g, 0.121 mmol, 0.2 eq) was added. The mixture was heated in a nitrogen atmosphere at 110° C. for 2 h, when complete conversion was observed by LC-MS. 3-methoxypyridine-5-boronic acid pinacol ester was added (0.284 g, 1.21 mmol, 2 eq) followed by Pd(dppf)Cl2.DCM (0.085 g, 0.121 mmol, 0.2 eq) and a saturated solution of K2CO3 (1 mL). The mixture was stirred in a microwave oven (120° C., 30 min), cooled to RT and concentrated. The residue was taken up in AcOEt and n-BuOH and washed with water. The organic phase was separated, dried (Na2SO4), filtered and concentrated, and the crude was purified by flash chromatography (SiO2, DCM/EtOAc) and, subsequently, by preparative HPLC (RP-C18, ACN/water) to give the desired product. HPLC-MS (10-95% B in 4 min at 0.5 mL+2 min 100% B, flow 0.8 mL/min, 50° C.): tR=4.09 min, [M+H]+ m/z 369.1; 1H-NMR (DMSO-d6): δ=8.82 (1H, d, J=1.5 Hz), 8.21 (1H, d, J=2.7 Hz), 7.99 (1H, dd, J=2.7, 1.5 Hz), 7.94 (1H, s), 7.52 (1H, dd, J=8.4, 2.1 Hz), 7.46 (1H, d, J=2.1 Hz), 7.12 (1H, d, J=8.4 Hz), 3.88 (3H, s), 3.83 (3H, s), 3.81 (3H, s) ppm.

Provenance & Evidence