Sodium Carbonate → 2-(2-methoxypyrimidin-5-yl)-7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 2-chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine from Example 104 (50 mg, 0.18 mmol), 2-methoxypyrimidin-5-ylboronic acid (42 mg, 0.27 mmol), Pd(PPh3)2Cl2 (12 mg, 0.02 mmol) and sodium carbonate (0.5 mL, 0.5 mmol, 1M aqueous solution) in acetonitrile (1.5 mL) then evacuated and back filled with nitrogen before being heated at 120° C. using microwave irradiation. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with methanol and the product eluted with 2M ammonia in methanol. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by trituration with diethyl ether affording 110 as a white solid (30 mg, 17%). LCMS: RT=4.18 min, [M+H]+=360. 1H NMR (400 MHz, CDCl3): δ 9.33 (2H, s), 4.07 (3H, s), 3.92 (2H, s), 3.83 (8H, s), 1.47 (6H, s)

Provenance & Evidence