A solution of methyl 5-chloro-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzoate (120 mg, 0.403 mmol) in MeOH (2 mL) was treated with 6 N NaOH (2 mL). The reaction was stirred for 2 h at RT, at which time it was concentrated in vacuo. The residue was suspended in water, acidified with 6 N HCl, filtered and dried. The resultant product was dissolved in DMF (4.0 mL) and treated with 3-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one, hydrochloride (76 mg, 0.403 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (82 mg, 0.604 mmol), EDC (116 mg, 0.604 mmol) and N-methylmorpholine (177 μl, 1.612 mmol). The reaction was stirred for 3 h at RT, at which time it was poured into saturated sodium bicarbonate solution and extracted with DCM (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give 5-chloro -N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-2-methyl-3-((1-methylpiperidin -4-yl)oxy)benzamide (0.050 g, 0.120 mmol, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.54-1.74 (m, 2 H) 1.80-1.94 (m, 2 H) 2.06 (s, 3 H) 2.12-2.22 (m, 6 H) 2.25 (d, J=9.60 Hz, 2 H) 2.31 (s, 3 H) 4.19 (d, J=5.05 Hz, 2 H) 4.48 (br. s., 1 H) 5.87 (s, 1 H) 6.79 (d, J=2.02 Hz, 1 H) 7.10 (d, J=2.02 Hz, 1 H) 8.21 (t, J=4.93 Hz, 1 H) 11.00 (s, 1 H). MS(ES) [M+H]+ 418.3.
