Table 2.

Optimization of the reaction conditions for the coupling of compound 2 with 1-Boc-piperazine.

entry	solvent	conditionsa	yield of 6b	yield of 8b
1	CH2Cl2	reflux, 48 h	93%	trace
2	CH2Cl2	reflux, 48 h, microwave	93%	trace
3	acetone	reflux, 48 h	93%	trace
4	THF	reflux, 48 h	81%	19%
5	EtOAc	reflux, 48 h	37%	61%
6	acetonitrile	reflux, 10 h	12%	88%
7	DMF	reflux, 5 h, 130 oC	0	0
8	acetonitrile	reflux, 10 h, 1-Boc-piperazine (2.5 mmol)	0	95%

^a2 (1.0 mmol), EDCl (1.2 mmol), NEt₃ (1.2 mmol), HOBt (1.2 mmol) and 1-Boc-piperazine (1.2 mmol) were dissolved in 10 mL of solvent for the indicated time. ^bIsolated yield.