Hydrochloric Acid → 3-(5-amino-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(5-amino-2-methylphenyl)-7-chloro-1-methyl-1,6-naphthyridin-2-one 8 (0.53 mmol) in dioxane (3 mL) is added triphenylphosphine (0.08 mmol), Pd2(dba)3 (16 umol) and trimethylaluminum (0.8 mL of a 2.0 molar solution in toluene). The mixture is degassed for 10 minutes then the reaction vial sealed and heated via microwave for 10 minutes at 150° C. The reaction is cooled to rt and poured into 1M HCl (30 mL) and washed with EtOAc. The aqueous layer is made basic with 3M NaOH and extracted with EtOAc (3×20 mL). The combined organic layers are dried over magnesium sulfate, filtered and reduced to dryness. The crude yellow oil is purified by flash chromatography on silica with dichloromethane 3-5% MeOH as eluant to yield a yellow glassy solid 15. 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.63 (s, 1H), 7.08 (s, 1H), 7.05 (d, J=8.4 Hz, 1H), 6.65 (dd, J=8.4, 2.4 Hz, 1H), 6.57 (d, J=2.4 Hz, 1H), 3.72 (s, 3H), 2.70 (s, 3H), 2.11 (s, 3H). MS (m/z) (M+1)+: 280.1.

Provenance & Evidence