Ammonium Hydroxide → 1-(2-Amino-2-oxoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

Participants

Reaction Steps

A solution of HATU (1.14 g, 3 mmol) in DMF (4 mL) was added in portions to a stirred suspension of [7-[(4-fluorophenyl)methyl]-4-hydroxy-3-({[2-(methyloxy)ethyl]amino}carbonyl)-2-oxo-1,5-naphthyridine-1(2H)-yl]acetic acid (1 g, 2.3 mmol) in 29% ammonium hydroxide (0.4 mL, 2.9 mmol), TEA (0.4 mL, 2.9 mmol) and DMF (4 mL) at 60° C. The mixture was stirred 40 min at rt and additional HATU (350 mg, 0.92 mmol), 29% ammonium hydroxide (0.15 mL, 1 mmol) and DMF (3 mL) were added. Stirring was continued 20 min and the suspension was diluted with water and filtered. The filter cake was washed with water and EtOH; then dried in a vacuum oven to afford the product as a white solid: 1H NMR (d6-DMSO) δ 10.25 (1H, t, J=5 Hz), 8.52 (1H, d, J=1 Hz), 7.83 (1H, s), 7.64 (1H, br s), 7.33 (2H, dd, J=8.6, 5.7 Hz), 7.27 (1H, br s), 7.11 (2H, t, J=8.6 Hz), 4.83 (2H, s), 4.11 (2H, s), 3.50 (4H, m), 3.28 (3H, s); HRMS calcd for C21H21FN4O5+H+: 429.1574. Found: 429.1575.

Provenance & Evidence