Diisopropylethylamine → 3-(3-amino-4-fluorophenyl)-N-(4-methoxybenzyl)-N,2-dimethyl-1,6-naphthyridin-7-amine

Participants

Reaction Conditions

Reaction Steps

Treat a solution of 5-(7-chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluoroaniline (0.353 g, 1.227 mmol) and 4-methoxy-N-methylbenzylamine (0.371 g, 2.454 mmol) in NMP (6 mL) in a sealed tube with N,N-diispropylethylamine (DIEA) (0.429 mL, 2.454 mmol), sparge with argon and heat at 170° C. overnight. Add additional 4-methoxy-N-methylbenzylamine (0.371 g, 2.454 mmol) and heat at 185° C. for 24 h. Add more 4-methoxy-N-methylbenzylamine (0.15 g, 1 mmol) and heat the mixture overnight at 185° C. Cool to RT, dilute with EtOAc and wash with satd. NaHCO3, water, and then brine. Dry the organics over MgSO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (334 mg, 68%). 1H NMR (400 MHz, DMSO-d6): δ 8.95 (s, 1H), 7.95 (s, 1H), 7.15 (d, J=8.4 Hz, 2H), 7.05 (dd, J=11.5, 8.2 Hz, 1H), 6.85 (m, 2H), 6.78 (dd, J=8.8, 2.3 Hz, 1H), 6.71 (s, 1H), 6.54 (ddd, J=8.2, 4.4, 2.2 Hz, 1H), 5.24 (s, 2H), 4.85 (s, 2H), 3.69 (s, 3H), 3.08 (s, 3H), 2.47 (s, 3H); MS (ESI) m/z: 403.2 (M+H+).

Provenance & Evidence