反应详情

2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazole (from the previous step, 0.65 g, 2.50 mmol, 1 eq) was dissolved in DMF (9 mL), and NIS (0.41 g, 1.75 mmol, 0.7 eq) was added. The mixture was stirred at RT in an argon atmosphere. After 2 hours HPLC-MS analysis indicated incomplete conversion; 0.1 g of NIS was added, and the reaction mixture was stirred at RT overnight. Another 0.08 g of NIS was added, and after another 2 h of stirring at RT the reaction mixture was poured into 20 mL of aq. sodium thiosulfate (10%) and extracted with EtOAc. The combined organic layers were washed with water, dried (Na2SO4) and concentrated, and the residue (0.888 g) was purified by column chromatography (SiO2, cyclohexane/20-100% EtOAc) to afford the desired product (white solid, 0.336 g, 36% yield, 2 steps). HPLC-MS: (10-95% B in 4 min, 0.5 mL/min+2 min 100% B, 0.7 mL/min): tR=4.42 min, [M+H]+ m/z 387.9; 1H NMR (300 MHz, DMSO) δ/ppm 7.50 (dd, J=2.2, 8.4, 1H), 7.42 (d, J=2.1, 1H), 7.37 (s, 1H), 7.16 (d, J=8.5, 1H), 3.89 (s, 3H), 3.86 (s, 3H).

1. stirringthe reaction mixture was stirred at RT overnight
2. stirringafter another 2 h of stirring at RT the reaction mixture
3. extractionextracted with EtOAc
4. washThe combined organic layers were washed with water
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated
7. customthe residue (0.888 g) was purified by column chromatography (SiO2, cyclohexane/20-100% EtOAc)