Table 1.

Formation of piperazinyl amide 4: selected optimization reactions.

entry	conditionsa	yield of 4b
1	piperazine (3 equiv), 0 °C	21%
2	piperazine (6 equiv), 0 °C	28%
3	piperazine (10 equiv), 0 °C	33%
4	compound 3 (in 30 mL DCM) was added dropwise to the solution of piperazine (10 equiv), 0 °C	36%
5	compound 3 (in 100 mL DCM) was added dropwise to the solution of piperazine (10 equiv), 0 °C	39%
6	compound 3 (in 100 mL DCM) was added dropwise to the solution of piperazine (10 equiv), 25 °C	32%

^aReaction performed on a 0.90 mmol scale of acyl chloride 3. ^bIsolated yield.