Potassium Carbonate → HCID 86694439, compound

Participants

Reaction Steps

The mixture of 6-bromo-8-(2-cyclopropyl-6-fluorobenzyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (11, 120 mg, 0.21 mmol), ethynyltrimethylsilane (74 μl, 0.53 mmol), PdCl2(PPh3)2 (15 mg, 0.02 mmol) and CuI (3 mg, 0.02 mmol) in triethylamine (1.5 mL) was irradiated for 90 min at 80° C. in a microwave reactor. The reaction mixture was cooled, filtered through Celite (washed with triethylamine and dichloromethane) and evaporated to dryness. The crude material was purified by column chromatography over silica eluting with chloroform. The isolated material (87 mg) was suspended in 5 mL methanol, potassium carbonate (38 mg, 0.28 mmol) was added and the yellow suspension was stirred for 30 min at room temperature and evaporated. The solid residue was partitioned between water (10 mL) and dichloromethane (2×15 mL). The combined organic layers were washed with brine (15 mL), dried over sodium sulfate, filtered, evaporated and purified by filtration through silica with chloroform:methanol (95:5) followed by preparative HPLC. The title compound (19 mg, 0.04 mmol, 17%) was obtained as a yellow powder. ESMS m/z 509 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.50 (s, 1H) 7.79 (s, 1H) 7.34 (d, J=8.5 Hz, 2H) 7.19 (br. s, 1H) 7.07-7.14 (m, 1H) 6.82-6.92 (m, 3H) 6.78 (dd, J=10.5, 8.8 Hz, 1H) 5.80 (s, 2H) 3.28 (s, 1H) 3.16-3.25 (m, 4H) 2.60-2.69 (m, 4H) 2.39 (s, 3H) 2.16-2.27 (m, 1H) 0.80-0.87 (m, 2H) 0.61-0.68 (m, 2H).

Provenance & Evidence