Sodium Carbonate → 5-(1-Morpholin-4-yl-5,6,8a,9-tetrahydro-8h-7,10-dioxa-2,4,4b-triaza-phenanthren-3-yl)-pyrimidin-2-ylamine

Temperature

120 °C

A mixture of 3-chloro-1-morpholin-4-yl-5,6,8a,9-tetrahydro-8H-7,10-dioxa-2,4,4b-triaza-phenanthrene (45 mg, 0.144 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (60 mg, 0.271 mmol), PdCl2(PPh3)2 (10 mg, 0.014 mmol) and sodium carbonate (460 μL, 0.46 mmol, 1M aqueous solution) in acetonitrile (2 mL) was degassed and heated at 120° C. for 30 mins in a microwave reactor. 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 reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-98%) affording 121 as a white solid (3 mg, 6%). LCMS (method B): RT=3.08 min, [M+H]+=372. 1H NMR (400 MHz, CDCl3): δ 9.11 (2H, s), 5.18 (2H, broad s), 4.55 (1H, dd, J=13.5, 2.4 Hz), 4.22 (1H, dd, J=10.8, 3.1 Hz), 4.05 (1H, dd, J=11.5, 3.5 Hz), 3.88 (2H, m), 3.81 (4H, m), 3.69-3.56 (6H, m), 3.29 (1H, t, J=11.5 Hz), 3.02 (1H, m).

1. customwas degassed
2. washwas washed with methanol
3. washthe product eluted with 2M ammonia in methanol
4. concentrationconcentrated in vacuo
5. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-98%)

ORD record

ord-437266e6d8164daaa2b01514d31be7d3

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08883799B2