General procedure for the synthesis of 5-(methoxymethyl)-1,3,4-thiadiazol-2-amine a25: Aminothiourea a24 (40 g, 0.44 mol, 1 eq.) was suspended in dioxane (400 mL) at room temperature, followed by a one-time addition of methoxyacetic acid (39.56 g, 0.44 mol, 1 eq.). The reaction mixture was heated to 80 °C and phosphorus trichloride (67.54 g, 0.44 mol, 1 eq.) was added slowly and dropwise over 1.5 hours. After completion of the reaction (4 h), water was added and the solution was neutralized to pH 6-7 using sodium hydroxide pellets. after extraction with EtOAc/iPrOH (9/1) mixed solvent, the solvent was evaporated in vacuum and the residue was recrystallized by MeTHF/iPrOH mixed solvent to afford pure 5-(methoxymethyl)-1,3,4-thiadiazol-2-amine a25 (51 g, yield 81%).LC-MS (MH+): 146.
