2 g (9.08 mmol) of (4-amino-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid, 1.692 g (9.08 mmol) of tert-butyl 1-piperazinecarboxylate, 1.916 g (10 mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, 1.35 g (10 mmol) of 1-hydroxy-1H-benzotriazole and 3.8 ml (27 mmol) of triethylamine are stirred in 200 ml of dichloromethane at RT overnight. The reaction mixture is then washed with sat. aqu. NaHCO3 solution, dried over MgSO4, filtered and concentrated. The crude product (3.05 g) can be used without further purification for the next step or, if required, be chromatographed on silica gel (CH2Cl2/EtOH=1/0 to 2/1+0.1% conc. aqueous ammonia solution) for purification.
