Sodium Thiosulfate → 2-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

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Reaction Steps

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).

Provenance & Evidence