N-3,4-Dimethoxybenzyl or N-DMPM

Protection

A mixture of 5-amino-1,2,4-thiadiazole (1g, 9.89 mmol) and 2,4-dimethoxybenzaldehyde (1.81g, 10.9 mmol) in toluene (30ml) was refluxed under Dean-Stark conditions for 2 hours. The reaction mixture was evaporated and the residue taken up in methanol (25ml), sodium borohydride (600 mg, 15.9 mmol) was added carefully in small portions (vigorous effervescence after each addition), and the reaction was left to stir for 18 hours at ambient temperature. A 2M aqueous solution of hydrogen chloride (1 mL) was added followed by a 2M aqueous solution of sodium hydroxide (10 mL). The bulk of the methanol was evaporated, water (20 mL) was added and the mixture extracted with ethyl acetate (2*30mL). The combined organic phase was washed with brine (20 mL), dried and concentrated in vacuo. The residue was purified by silica gel column chromatography to furnish a semi-solid residue that was re-evaporated from heptane. tert-Butylmethyl ether (2-3 mL) was added, followed by heptane (2-3 mL). The resulting solid was collected by filtration, washed with heptane and dried to afford the title compound (1.22 g). 

Patent reference: WO2012004743

Deprotection

N-DMPM protective compound was dissolved in 1,4-dioxane (1.5 mL) and a 4M solution of hydogen chloride in 1,4-dioxane (2.4 mL) added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the resulting residue purified by reverse phase preparative HPLC to afford the title compound as a white solid (120 mg, 42%). 

Patent reference: WO2012004743

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