To a solution of (S)-tert-butyl 2-((cyanoimino)(methylthio)methylamino)-3-cyclohexylpropyl(methyl)carbamate (200 mg, 0.543 mmol) in DMF (8 mL) and Et3N (0.5 mL) was added methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate (178 mg, 0.543 mmol). The mixture was heated at 100-110° C. for 48 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water (30 mL×4), dried over Na2SO4 and concentrated to give the residue, which was purified by column to give methyl 2-((R)-(3-chlorophenyl)((R)-1-(N′-cyano-N—((S)-1-cyclohexyl-3-(N-methyl-N-(tert-butoxycarbonyl)amino)propan-2-yl)carbamimidoyl)piperidin-3-yl)methoxy)ethylcarbamate (8 mg, 2%).
