Triethylamine → 6-(3-[1,3]Dioxolan-2-yl-5-methyl-phenoxy)-1-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-1H-pyrimidine-2,4-dione

Participants

Reaction Steps

To a stirred solution of 2-fluoro-6-(p-methoxybenzylamino)-4-pyridine-methanol (664 mg, 2.53 mmol) in chloroform (25 ml) at 0° C. (ice bat), was added triethylamine (532 μl, 3.8 mmol) followed by methanesulfonyl chloride (228 μl, 3.0 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo and mixed with 6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione (842 mg, 2.53 mmol), anhydrous powdered potassium carbonate (349 mg, 2.53 mmol), and lithium iodide (339 mg, 2.53 mmol). Anhydrous DMF (25 ml) was then added into the mixture and stirred for overnight at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through a celite pad, and the pad was washed with dichloromethane. The combined filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 771 mg (53%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.12 (6H, d, J=7.2 Hz), 2.30 (3H, s), 2.73 (1H, m), 3.79 (3H, s), 3.94-4.14 (4H, m), 4.32 (2H, d, J=5.4 Hz), 4.71 (2H, s), 5.00 (1H, t, J=5.4 Hz), 5.67 (1H, s), 5.95 (2H, s), 6.59 (1H, s), 6.81-6.91 (3H, m), 7.02 (1H, s), 7.21-7.29 (2H, m), 9.06 (1H, s).

Provenance & Evidence