Sodium Carbonate → 5-(7-Cyclopropyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 2-chloro-7-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (205 mg, 0.49 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (324 mg, 1.47 mmol), Pd(PPh3)2Cl2 (51 mg, 0.07 mmol), sodium carbonate (2.41 mL, 2.41 mmol, 1M aqueous solution) and acetonitrile (2.5 mL). The vessel was sealed then evacuated and back filled with argon (×3) before being heated at 120° C. for 30 minutes using microwave irradiation. The reaction mixture was filtered and the filtrate concentrated in vacuo. The resultant residue was purified by column chromatography (SiO2, gradient 0-4% methanol in DCM), then triturated in diethyl ether/pentane. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient methanol 10-98%) affording 118 as an off white solid (4.5 mg, 3%). LCMS: RT=3.52 min, [M+H]+=357. 1H NMR (400 MHz, DMSO-d6): δ 8.91 (2H, s), 7.01 (2H, s), 4.40 (1H, dd, J=11.38, 2.41 Hz), 4.01 (1H, dd, J=11.41, 7.52 Hz), 3.80-3.60 (9H, m), 1.11-0.98 (1H, m), 0.69-0.41 (4H, m).

Provenance & Evidence