Potassium Carbonate → 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-N,N-dimethyl-acetamide

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 TFA salt (386 mg, 0.76 mmol) in THF (5 mL) was added potassium carbonate (210 mg, 1.52 mmol) followed by 2-chloro-N,N-dimethylacetamide (102 mg, 0.84 mmol). The reaction mixture was stirred for 65 hours before being diluted with DCM and water. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM) then freeze-dried from methanol and water to give 509 as a white solid (158 mg, 43%). LCMS: RT=3.33 min, [M+H]+=481. 1H NMR δ (ppm) (DMSO-d6): 8.27 (1 H, d, J=8.20 Hz), 8.09 (1 H, d, J=0.59 Hz), 7.09 (1 H, dd, J=8.25, 1.83 Hz), 6.93 (1 H, d, J=1.77 Hz), 5.83-5.81 (1 H, m), 4.35 (2 H, t, J=5.02 Hz), 3.41 (2 H, t, J=5.05 Hz), 3.15 (2 H, s), 3.05 (3 H, s), 2.93 (2 H, d, J=10.95 Hz), 2.82 (3 H, s), 2.48-2.44 (1 H, m), 2.16-2.13 (2 H, m), 1.81-1.70 (2 H, m), 1.66-1.64 (2 H, m), 1.54 (6 H, d, J=6.59 Hz)

1. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
2. concentrationconcentrated in vacuo
3. customThe resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM)
4. dry with materialthen freeze-dried from methanol and water

ORDレコード

ord-f68b5cdd4ead4de9a710b4276834843d

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08952043B2