6-Iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (1.50 g) is dissolved in CH2Cl2 (0.5 L). To this is added diphenyl chloridophosphate (1.5 mL) and triethyl amine (1.7 mL). The resulting mixture is stirred at room temperature for 2 h, followed by the addition of 4-chlorobenzyl amine (1.2 mL). The reaction is stirred for additional 3 h, then washed with 1N HCl, 1N NaOH, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, CH2Cl2/MeOH 19/1) and the product is then triturated with MeOH to afford 592 mg (29%) of N-(4-chlorobenzyl)-6-iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide. Physical characteristics are as follows: 1H NMR (CDCl3) δ 10.20, 9.01, 8.81, 7.32-7.27, 4.62, 4.13, 3.96; 13C NMR (CDCl3) δ 175.24, 164.41, 162.95, 159.66, 148.69, 147.78, 147.69, 137.26, 132.85, 128.93, 128.69, 118.76, 113.68, 55.77, 42.58, 39.12; IR (diffuse reflectance) 2296, 1908, 1665, 1613, 1593, 1570, 1544, 1507, 1491, 1460, 1447, 1386, 1286, 1278, 809, cm−1; MS (FAB) m/z 484 (MH+), 486, 485, 484, 344, 343, 217, 133, 127, 125, 55; Anal. calcd for C18H15ClIN3O3: C, 44.70; H, 3.13; N, 8.69. Found: C, 44.38; H, 3.17; N, 8.62.
