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

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 5-iodo-N-(6-methoxypyridin-3-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (141 mg, 0.355 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (153 mg, 0.355 mmol), copper(I) iodide (14 mg, 0.071 mmol), cesium fluoride (108 mg, 0.710 mmol), tetrakis(triphenylphosphine)palladium(0) (41.0 mg, 0.035 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 (10 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 brown oil. The crude product was purified by silica gel chromatography eluting with 60% EtOAc/hexanes to give N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (28 mg, 0.068 mmol, 19.22% yield). 1H NMR (300 MHz, CDCl3) δ 11.74 (s, 1H); 9.45 (s, 1H); 8.49 (s, 1H); 8.13 (dd, J=8.92, 2.34 Hz, 1H); 6.77 (d, J=8.77 Hz, 1H); 3.95 (s, 3H); 3.58-3.76 (m, 4H); 2.59 (s, 3H); 2.57 (s, 3H); 1.93-2.09 (m, 4H). m/z (ESI, +ve ion) 411.0 (M+H)+.

Provenance & Evidence