Cesium fluoride → N2-cyclopentyl-N4-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamine

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with N2-cyclopentyl-5-iodo-N4-(6-methoxypyridin-3-yl)pyrimidine-2,4-diamine (145 mg, 0.353 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (152 mg, 0.353 mmol), copper(I) iodide (14 mg, 0.071 mmol), cesium fluoride (107 mg, 0.705 mmol), tetrakis(triphenylphosphine)palladium(0) (40.7 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 20 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 (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a black solid. The crude product was purified by silica gel chromatography eluting with 50% EtOAc/hexanes to give N2-cyclopentyl-N4-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamine (52 mg, 0.122 mmol, 34.7% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ 11.46-11.87 (m, 1H); 9.15-9.62 (m, 1H); 8.26-8.63 (m, 1H); 7.84-8.26 (m, 1H); 6.77 (d, J=8.77 Hz, 1H); 5.11-5.52 (m, 1H); 4.12-4.56 (m, 1H); 3.95 (s, 3H); 2.59 (d, J=6.87 Hz, 6H); 1.87-2.21 (m, 2H); 1.56-1.87 (m, 4H). m/z (ESI, +ve ion) 425.1 (M+H)+.

Provenance & Evidence