Chloroacetaldehyde → 2-(Methylsulfanyl)imidazo[2,1-b][1,3,4]thiadiazole

Participants

Reaction Steps

2-Amino-5-methylthio-1,3,4-thiadiazole (10.00 g; 67.92 mmol; 1.00 eq.) was reluxed in 1-butanol (100.00 ml) until complete dissolution of starting material. Then, chloroacetaldehyde (21.91 ml; 169.81 mmol; 2.50 eq.) was slowly added and the reaction was refluxed for 2 h. Diisopropyethylamine (11.63 ml) was slowly added over 2 h using a syringe pump. After 18 h, the reaction was allowed to cool to room temperature. Then, water was added and the aqueous phase was extracted 4 times with EtOAc. The combined organics were washed with brine, dried over MgSO4 to give 17 g of a viscous brown oil. The crude was purified by flash chromatography (preabsorption using MeOH an silica) using 95/5 dichloromethane/methanol. The combined fractions gave 3.05 g of the desired product as a pale orange solid.

Provenance & Evidence