Cesium fluoride → 1-(5-(5-Fluoro-6-methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine (151 mg, 0.384 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (36.6 mg, 0.077 mmol, Aldrich, St. Louis, Mo.), palladium diacetate (8.63 mg, 0.038 mmol, Aldrich, St. Louis, Mo.), copper(I) iodide (15 mg, 0.077 mmol, Aldrich, St. Louis, Mo.), cesium fluoride (117 mg, 0.769 mmol, Alfa Aesar) and tributyl(1-ethoxyvinyl)tin (0.195 mL, 0.577 mmol, Aldrich, St. Louis, Mo.) in dioxane (3 mL) was stirred at 100° C. for 18 h. The mixture was cooled down to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2 (2×30 mL). The combined organic extracts were washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography, eluting with 10% EtOAc/CH2Cl2 to give 1-(5-(5-fluoro-6-methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanone (102 mg, 0.255 mmol, 66.3% yield). 1H NMR (300 MHz, CDCl3) δ 2.66 (s, 3H) 2.71 (s, 3H) 2.81 (s, 3H) 4.05 (s, 3H) 8.04-8.33 (m, 3H) 8.92 (s, 1H) 12.99 (s, 1H). m/z (ESI, +ve ion) 401.0 (M+H)+.

Provenance & Evidence