tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate → 4-(4-benzylphenylamino)-6-(2-(1-N-BOC-piperazin-4-yl)ethylamino)-1,7-naphthyridine-3-carbonitrile

Participants

Reaction Steps

A microwave vial was charged with 4-(4-benzylphenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.100 g, 0.282 mmol), 1-N-BOC-4-(2-aminoethyl)piperazine and 2 mL THF, crimp-sealed, and heated in a microwave reactor at 180° C. for 35 minutes, until TLC analysis (5% MeOH in CH2Cl2) showed disappearance of the 6-fluoronaphthyridine. This process was repeated with 3 additional aliquots of the fluoronaphthyridine (0.120 g, 0.100 g, 0.100 g), and the contents of all 4 vials were then combined, partitioned between 50 mL each EtOAc and brine, and worked up as described above for the synthesis of WAY-191220. The crude product was purified by flash chromatography over silica gel (5% MeOH in CH2Cl2) and lyophilized to give pure 4-(4-benzylphenylamino)-6-(2-(1-N-BOC-piperazin-4-yl)ethylamino)-1,7-naphthyridine-3-carbonitrile (0.151 g, 23% yield): 1H NMR (400 MHz, DMSO-D6) δ 1.39 (s, 9 H) 2.34-2.44 (m, 4 H) 2.57 (t, J=6.6 Hz, 2 H) 3.21-3.42 (m, 6 H) 3.99 (s, 2 H) 6.59 (t, J=5.3 Hz, 1 H) 7.03 (s, 1 H) 7.14-7.34 (m, 9 H) 8.22 (s, 1 H) 8.81 (s, 1 H) 9.56 (s, 1 H).

Provenance & Evidence