反应详情

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (0.125 g, 0.312 mmol, 1 eq), 2-cyanopyridine-5-boronic acid pinacol ester (0.095 g, 0.414 mmol, 1.33 eq), Pd(dppf)Cl2.DCM (0.008 g, 0.009 mmol, 0.03 eq) and cesium carbonate (0.305 g, 0.935 mmol, 3 eq) in DME (4 mL) and water (0.1 mL) was heated in the microwave oven (45 min, 130° C.), cooled to RT, diluted with water, extracted with EtOAc and washed with brine. The organic layers were dried (MgSO4), filtered and concentrated, and the residue was purified by silica gel chromatography (0-100% DCM in hexane, then 0-3% MeOH in DCM). Product fractions were concentrated to give a solid that was further purified by preparative HPLC affording the pure product (0.002 g, 2% yield). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min): tR=5.52 min, [M+H]+ m/z 378.1. 1H NMR (300 MHz, CDCl3) δ/ppm 9.16 (d, J=1.5, 1H), 8.18 (dd, J=8.4, 2.2, 1H), 7.82-7.67 (m, 1H), 7.41-7.28 (m, 2H), 6.89 (d, J=8.4, 0H), 3.91 (s, 3 H), 3.89 (s, 3 H), 2.54 (s, 1H).

1. extractionextracted with EtOAc
2. washwashed with brine
3. dry with materialThe organic layers were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customthe residue was purified by silica gel chromatography (0-100% DCM in hexane
7. concentrationProduct fractions were concentrated
8. customto give a solid
9. customthat was further purified by preparative HPLC