Diisopropylethylamine → Methyl ({[7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridin-4-yl]carbonyl}amino)acetate

Participants

Reaction Steps

To a mixture of 7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylic acid (40 mg, 0.096 mmol), N,N-diisopropylethylamine (0.067 mL, 0.39 mmol), and catalytic DMAP in 2.5 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.069 mL, 0.116 mmol). After 6 min at rt, glycine methyl ester hydrochloride (18.1 mg, 0.144 mmol) was added and the reaction stirred at rt for 4 hours. The reaction was quenched with aqueous NaHCO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, aqueous NaHCO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. This material was chromatographed eluting with CHCl3/EtOAc plus 10% MeOH to give the title compound as a light yellow solid (30 mg, 64%). 1H NMR (CDCl3) δ: 8.55 (s, 1H), 8.47 (s, 1H), 7.93 (s, 1H), 7.53 (d, J=11.4 Hz, 2H), 7.47 (d, J=7.3 Hz, 1H), 7.33-7.40 (m, 1H), 7.20-7.32 (m, 2H), 7.11 (d, J=7.9 Hz, 1H), 7.03 (d, J=7.6 Hz, 1H), 6.62 (t, J=5.1 Hz, 1H), 4.47 (s, 2H), 4.24 (d, J=5.3 Hz, 2H), 3.81 (s, 3H), 3.56-3.61 (m, 2H), 3.20 (t, J=5.6 Hz, 2H), 2.85-2.99 (m, 1H), 1.27 (d, J=6.7 Hz, 6H)

Provenance & Evidence