Morpholine → 5-((S)-6-Morpholin-4-yl-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalen-8-yl)-pyrimidin-2-ylamine

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-6,8-dichloro-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalene (290 mg, 1.18 mmol), morpholine (275 μL, 3.14 mmol) and triethylamine (242 μL, 1.74 mmol) in IMS (11 mL) was heated at 140° C. for 20 mins in a microwave reactor, then concentrated in vacuo. The resulting residue re-dissolved in acetonitrile (2 mL) and 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (500 mg, 2.26 mmol), PdCl2(PPh3)2 (88 mg, 0.125 mmol) and sodium carbonate (4 mL, 4.0 mmol, 1M aqueous solution) were added. The reaction mixture 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 gradient acetonitrile 5-60%) affording 122 as a white solid (30 mg, 8%). LCMS (method B): RT=3.34 min, [M+H]+=356. 1H NMR (400 MHz, CDCl3): δ 9.15 (2H, s), 5.14 (2H, broad s), 4.48 (1H, dd, J=10.4, 3.5 Hz), 3.87-3.68 (10H, m), 3.62 (1H, m), 3.31 (1H, t, J=10.1 Hz), 2.21-1.94 (3H, m), 1.50 (1H, m).

Provenance & Evidence