(2S)-N-cyclobutylpyrrolidine-2-carboxamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.00 g 4-(2-{[5-((R)-1-Carboxy-ethoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-acetyl)-piperazine-1-carboxylic acid butyl ester in 40 ml DMF were added 521 μl DIPEA and 758 mg HATU. After 20 minutes 336 mg (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide were added and the reaction mixture stirred for 3 h. After evaporation of the solvent the crude product was dissolved in dichloromethane and extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were immediately lyophilized to yield the pure product which was taken up in dichloromethane and washed once with aqueous NaHCO3. The residue obtained after evaporation of the solvent was lyophilized again to give the title compound. Yield: 517 mg MS (ES+): m/e=652. After evaporation of the solvent the crude product was dissolved in dichloromethane extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3 The crude product obtained after evaporation of the solvent was purified by preparative HPLC ( C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) The fractions containing the product to yield the pure product which washed once with aqueous NaHCO3 The residue obtained after evaporation of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.00 g (S)-2-Cyclobutylcarbamoyl-pyrrolidine-1-carboxylic acid benzyl ester in 120 ml ethanol were added 1.0 g Pd/C (10%) and the suspension stirred under an atmosphere of hydrogen (3 bar) for 12 h. The reaction mixture was filtrated over a plug of Celite, washed with ethanol and concentrated to give the crude product which was used in the subsequent reaction. Yield: 3.3 g. The reaction mixture was filtrated over a plug of Celite washed with ethanol concentrated