To a solution of 2.000 g 4-((S)-4-tert-Butoxycarbonyl-2-{[5-carboxymethoxy-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester in 20 ml DMF were added 0.506 g HOBt, 1.2 ml DIPEA and 0.798 g L-proline benzyl ester hydrochloride at RT. Then 0.633 g EDC was added portionwise and the suspension stirred at RT for 12 h. The reaction mixture was diluted with ethyl acetate and subsequently extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product thus obtained was used in the subsequent reaction.
