3-(Trifluoromethyl)aniline → Methyl 7-[3-({[3-(trifluoromethyl)phenyl]amino}carbonyl)phenyl]-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylate

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Reaction Steps

To a mixture of 3-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid (63 mg, 0.20 mmol), triethylamine (0.084 mL, 0.60 mmol), and catalytic DMAP in 3.0 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.143 mL, 0.24 mmol). After 5 min at rt, 3-(trifluoromethyl)aniline (0.037 mL, 0.30 mmol) was added and the reaction stirred at rt for 18 hours. The reaction was quenched with aqueous NaHCO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, dilute aqueous NaHCO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. This material was chromatographed eluting with CHCl3/EtOAc to give the title compound as a yellow solid (50 mg, 55%). 1H NMR (Acetone-d6) δ: 9.75 (br. s., 1H), 8.89 (s, 1H), 8.66 (s, 1H), 8.32 (s, 1H), 8.09 (d, J=7.9 Hz, 1H), 7.69 (s, 1H), 7.60 (t, J=7.9 Hz, 1H), 7.37-7.47 (m, 3H), 7.28-7.34 (m, 1H), 4.61 (s, 2H), 3.92 (s, 3H), 3.67-3.73 (m, 2H), 3.37 (t, J=5.9 Hz, 2H).

Provenance & Evidence