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

Temperature

60 °C

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 (310 mg, 0.61 mmol) in DMF (3.5 mL) was added 2(2-bromoethoxy)tetrahydro-2H-pyran (0.1 mL, 0.67 mmol) and potassium carbonate (290 mg, 2.10 mmol) and the reaction mixture stirred at 60° C. for 16 h. The reaction mixture was diluted with DCM and washed with sodium bicarbonate (sat aq.) 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) to give 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-piperidin-4-yl}-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (106 mg, 33%). LCMS: RT=3.71 min, [M+H]+=524 1H NMR 400 MHz (DMSO-d6) δ: 8.27 (1 H, d, J=8.19 Hz), 8.09 (1 H, d, J=0.58 Hz), 7.09 (1 H, dd, J=8.26, 1.82 Hz), 6.92 (1 H, d, J=1.78 Hz), 5.82-5.82 (1 H, m), 4.58 (1 H, t, J=3.52 Hz), 4.35 (2 H, t, J=5.02 Hz), 3.75-3.74 (2 H, m), 3.44-3.42 (4 H, m), 2.99 (2 H, t, J=10.97 Hz), 2.54 (2 H, t, J=6.17 Hz), 2.47 (1 H, s), 2.09 (2 H, t, J=11.61 Hz), 1.79-1.55 (6 H, m), 1.55 (6 H, d, J=6.59 Hz), 1.52-1.43 (4 H, m).

1. washwashed with sodium bicarbonate (sat aq.)
2. dry with materialdried (MgSO4)
3. concentrationconcentrated in vacuo

ORD record

ord-e0b7ee416fa34be9b1acf3080ff63e89

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952043B2