Synthesis of the cyclam-piperidinylnaphthalimide conjugates 8–10.

<p><i>Reagents and conditions</i>: (a) 4-bromoaniline, piperidine, 2-methoxyethanol, reflux, 72 h, 90%; (b) NaN₃, CuI, sodium ascorbate, DMEDA, THF/H₂O (7∶3), 12 h, 50%; (c) propargyl-tri-Boc cyclam, CuSO₄·5H₂O, sodium ascorbate, THF/H₂O (7∶3), rt for <b>13</b> and 50°C for <b>17</b>, 12 h, <b>14</b>: 96%, <b>18</b>: 92%; (d) (i) TFA/DCM/H₂O (90∶5∶5), rt, 6 h; (ii) Ambersep 900 hydroxide form, CH₃OH, rt, 15 min, <b>8</b>: 96%, <b>9</b>: 99%, <b>10</b>: 99%; (e) 2-aminoethanol, EtOH, reflux, 22 h, 92%; (f) PBr₃, pyridine, THF, 50°C, 16 h, 60%; (g) NaN₃, EtOH, reflux, 6 h, 80%; (h) trimethylsilylacetylene, CuI, triphenylphosphine, Pd(PPh₃)₄, Et₃N, pyridine, 85°C, o/n, 94%; (i) K₂CO₃, CH₃OH, rt, o/n, 97%; (j) 2-azidoethyl-tri-Boc cyclam, CuSO₄·5H₂O, sodium ascorbate, THF/H₂O (7∶3), 12 h, 66%.