Ethanolamine → HCID 67050584, compound

Temperature

85 °C

9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 6 (0.350 g, 0.894 mmol), ethanolamine (0.162 mL, 2.68 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.054 g, 0.093 mmol), and sodium carbonate (0.569 g, 5.37 mmol) were added to a nitrogen flushed flask. To the mixture was added toluene (20 mL) and nitrogen was bubbled through the reaction mixture for 2 minutes. To the reaction mixture was added Pd(OAc)2 (0.021 g, 0.093 mmol), then CO was bubbled through the reaction mixture for 1 minute and the reaction was placed under a CO balloon and stirred and heated at 85° C. for 18 hours. LCMS showed very little conversion from starting material to product. To the reaction mixture was added ethanolamine (0.162 mL, 2.68 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.054 g, 0.093 mmol), sodium carbonate (0.569 g, 5.37 mmol), and Pd(OAc)2 (0.021 g, 0.093 mmol), then CO was bubbled through the reaction mixture for 1 minute and the reaction was placed under a CO balloon and stirred and heated at 85° C. for 18 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc, and filtered through a pad of celite. The filtrate was concentrated under reduced pressure and diluted with EtOAc. The solution was washed sequentially with water, and brine, before drying over MgSO4 and concentrating under reduced pressure. The crude material was dissolved in DMF and purified by reverse phase HPLC provide 111 (3 mg, 8%). 1H NMR (400 MHz, DMSO) δ 8.92 (d, J=2.1, 1H), 8.37 (t, J=5.5, 1H), 8.08 (d, J=21.9, 1H), 7.75 (dd, J=8.4, 2.1, 1H), 7.12 (d, J=8.4, 1H), 5.83 (dt, J=13.0, 6.6, 1H), 4.70 (t, J=5.4, 1H), 4.42 (t, J=4.8, 2H), 3.56-3.44 (m, 4H), 3.38 3.33 (m, 2H), 1.57 (d, J=6.6, 6H). MS (ESI(+)): m/z 400.1 (M+H)

1. customwas bubbled through the reaction mixture for 2 minutes
2. customCO was bubbled through the reaction mixture for 1 minute
3. customCO was bubbled through the reaction mixture for 1 minute
4. stirringstirred
5. temperatureheated at 85° C. for 18 hours
6. temperatureThe reaction mixture was cooled to room temperature
7. additiondiluted with EtOAc
8. filtrationfiltered through a pad of celite
9. concentrationThe filtrate was concentrated under reduced pressure
10. additiondiluted with EtOAc
11. washThe solution was washed sequentially with water, and brine
12. dry with materialbefore drying over MgSO4
13. concentrationconcentrating under reduced pressure
14. dissolutionThe crude material was dissolved in DMF
15. custompurified by reverse phase HPLC

ORD record

ord-f83337cdbaba4ad9b8e5e3dbb362c8ae

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263633B2