A catalytic amount of TsOH (20 mg) was added to a solution of 1-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-ethanone obtained from Step 1 (233 mg, 1.20 mmol) and (2-amino-ethyl)-benzo[1,3]dioxol-5-ylmethyl-carbamic acid tert-butyl ester (565 mg, 1.92 mmol) in 1,4-dioxane (10 mL) under a nitrogen atmosphere at r.t. prior to heating at 65-70° C. for 4 h. The reaction was then cooled to r.t. and NaHB(OAc)3 (763 mg, 3.60 mmol) was added. After stirring for an additional hour, water was added and the solution was extracted with ethyl acetate (2×70 mL), washed with brine and dried over Na2SO4. Evaporation of the solvent gave a yellow residue which was dissolved in TFA/DCM (1:1, 6 mL) and stirred at room temperature for 30 min. The solvent was evaporated to afford a yellow solid. The crude product was diluted with EtOAc (100 mL), washed with 1M NaOH (50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to an orange solid. Purification was achieved using column chromatography (CH2Cl2 to 4:1 CH2Cl2/MeOH) to afford 31 mg (7%) of N-benzo[1,3]dioxol-5-ylmethyl-N′-[1-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-ethyl]-ethane-1,2-diamine as a white solid. [M+H]+ 372.97; 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.74 (s, 1H), 7.13 (s, 1H), 6.84 (s, 1H), 6.76 (m, 2H), 5.93 (s, 2H), 4.12 (q, 1H), 3.73 (d, 2H), 2.91-2.77 (m, 4H), 2.19 (br s, 2H), 1.54 (d, 3H).
