Potassium Carbonate → 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methoxy-ethyl)-piperidin-4-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 375 (300 mg, 0.59 mmol) in DMF (3.5 mL) was added 2-bromoethyl methyl ether (60 μL, 0.65 mmol) and potassium carbonate (285 mg, 2.07 mmol) and the reaction mixture stirred at 60° C. for 2 h. The reaction mixture was diluted with DCM and washed with saturated aqueous sodium bicarbonate, then water followed by brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% MeOH in DCM) followed by trituration in cyclohexane to give 511 (187 mg, 70%). LCMS: RT=3.42 min, [M+H]+=454. 1H NMR 400 MHz (DMSO-d6) δ: 8.23 (1 H, d, J=8.19 Hz), 8.05 (1 H, s), 7.04 (1 H, dd, J=8.22, 1.79 Hz), 6.88 (1 H, d, J=1.74 Hz), 5.77-5.76 (1 H, m), 4.31 (2 H, t, J=5.00 Hz), 3.44-3.34 (5 H, m), 3.20 (3 H, s), 2.93 (3 H, d, J=10.98 Hz), 2.02 (2 H, t, J=11.43 Hz), 1.71 (3 H, m), 1.64-1.53 (2 H, m), 1.50 (6 H, d, J=6.58 Hz)

Provenance & Evidence