Reaction Steps
Ethyl 4-(1-[2-dimethylaminoethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate and Ethyl 4-(6-[2-dimethyl-aminoethoxy]pyridin-3-yl)benzoate. To a cooled (0° C.) slurry of ethyl 4-(6-oxo-1,6-dihydropyridin-3-yl)benzoate [0.500 g, 2.06 mmol, reference example 36f] in THF:DMF [30 mL 5:1] is added 60% sodium hydride [0.247 g, 6.18 mmol]. After ten minutes added potassium iodide [2 mg] and 2-dimethylaminoethyl-chloride hydrochloride [Aldrich, 0.386 g, 2.68 mmol] and heated to 50° C. After twenty hours, quenched slowly with H2O [15 ml] and extracted with CH2Cl2. The organic extracts are combined and concentrated, then purified on an HPLC (40 to 60% AcCN in water with 0.1% TFA) to give ethyl 4-(1-[2-dimethylamino-ethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate [0.337 g, 38.2% yield] as the TFA salt and ethyl 4-(6-[2-di-methylaminoethoxy]pyridin-3-yl)benzoate [0.110 g, 12.5%] yield as the TFA salt. For ethyl 4-(1-[2-dimethylaminoethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate: 1H NMR (CD3OD): δ 1.40 (3H, t, J=7.8 Hz), 3.03 (6H, s), 3.62 (2H, t, J=5.9 Hz), 4.38 (2H, q, J=7.8 Hz), 4.49 (2H, t, J=5.9 Hz), 6.72 (1H, d, J=9.2 Hz), 7.68 (2H, d, J=8.8 Hz), 7.98 (1H, dd, J=9.2 Hz, 3.0 Hz), 8.07 (2H, d, J=8.8 Hz), 8.13 (1H, d, J=3.0 Hz). MS (ion spray) m/z 315 (M+H)+. For ethyl 4-(6-[2-dimethylaminoethoxy]pyridin-3-yl)benzoate: 1H NMR (CD3OD): δ 1.41 (3H, t, J=8.1 Hz), 3.02 (6H, s), 3.64 (2H, t, J=6.1 Hz), 4.39 (2H, q, J=8.1 Hz), 4.74 (2H, t, J=6.1 Hz), 7.01 (1H, d, J=9.4 Hz), 7.73 (2H, d, J=8.8 Hz), 8.07 (1H, dd, J=9.4 Hz, 2.5 Hz), 8.10 (2H, d, J=8.8 Hz), 8.51 (1H, d, J=2.5 Hz). MS (ion spray) m/z 315 (M+H)+.
