Cesium fluoride → 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 2-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (181 mg, 0.499 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (215 mg, 0.499 mmol), copper(I) iodide (19 mg, 0.100 mmol), cesium fluoride (250 mg, 0.998 mmol), tetrakis(triphenylphosphine)palladium(0) (57.7 mg, 0.050 mmol) and dioxane (3 mL). The reaction mixture was stirred and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 30 min. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The organic extract was 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 40% EtOAc/hexanes to give 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (87 mg, 0.231 mmol, 46.4% yield). 1H NMR (300 MHz, CDCl3) δ 11.82 (s, 1H); 9.48 (s, 1H); 8.37 (s, 1H); 8.08 (dd, J=9.28, 1.97 Hz, 1H); 6.83 (d, J=9.06 Hz, 1H); 3.96 (s, 3H); 2.67 (s, 3H); 2.64 (s, 3H). m/z (ESI, +ve ion) 376.0 (M+H)+.

Provenance & Evidence