2,6-Diaminopyridine → 6-(6-Aminopyridin-2-ylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A sealed tube was charged with DME (1.5 mL) and purged with argon. The vessel was then charged with 1G (0.050 g, 0.14 mmol), pyridine-2,6-diamine (0.039 g, 0.35 mmol), cesium carbonate (0.184 g, 0.57 mmol), copper(I) iodide (0.013 g, 0.071 mmol), Xantphos (0.016 g, 0.028 mmol), and Pd2(dba)3 (0.013 g, 0.014 mmol), in one portion. The resulting suspension was pump/purged with argon three times. The cap was placed on the vessel, and the suspension heated to 125° C. overnight. The solids were filtered off, and the filtrate was concentrated in vacuo. The crude product was dissolved in a small amount of DCM and charged to a 24 g silica gel cartridge which was eluted at 30 mL/min with a 20 min gradient from 100% DCM to 60% EtOAc/DCM, monitoring at 254 nm, affording 2A (0.014 g, 23% yield) as a tan solid. HPLC: Rt=3.62 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). MS (ES): m/z=427.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.19-8.28 (1 H, m), 7.41 (1H, s), 7.03-7.12 (3H, m), 6.96-7.03 (1H, m), 6.79-6.86 (2H, m), 6.13 (1H, s), 5.49 (2H, s), 3.68 (3H, s), 3.49-3.65 (3H, m), 2.45 (1H, d, J=3.78 Hz), 0.91-0.98 (2H, m), 0.74 (2H, m).

Provenance & Evidence