反应详情

1,2-Dibromoethane (0.03 ml, 10 mol %) was added to a stirred suspension of acid washed zinc dust (0.45 g, 7.0 mmol) in anhydrous DMF (3 ml) at 50° C. under nitrogen. After 5 min, neopentyl iodide (1.0 ml, 7.5 mmol) was added. The mixture was stirred for 2.5 h to give a grey-green milky solution. A mixture of 7-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.35 g, 0.866 mmol), tri-2-furylphosphine (0.08 g. 40 mol %) and tris(dibenzylideneacetone)dipalladium(0) (0.04 g, 5 mol %) in anhydrous DMF (2 ml) was stirred at 50° C. under nitrogen for 15 min followed by addition of the solution of organozinc reagent via syringe. After 2.5 h, the mixture was cooled, poured into water (100 ml) and extracted with dichloromethane (2×50 ml). The extracts were dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 2% methanol-dichloromethane, gave a brown solid that was recrystallised from ethyl acetate-diethyl ether to give 7-(2,2-dimethylpropyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.199 g, 58%) as a beige powder; 1H NMR (360 MHz, CDCl3) δ0.96 (9H, s), 2.61 (2H, s), 3.83 (3H, s), 5.47 (2H, s), 7.28 (1H, dd, J=10 and 10 Hz), 7.36 (1H, dd, J=8 and 8 Hz), 7.56-7.62 (1H, m), 7.83 (1H, s), 7.86 (1H, dd, J=8 and 8 Hz), 7.90 (1H, s); MS (ES+) m/e 396 [MH]+. Anal. Found C, 59.66; H, 5.69; N. 24.41%. C20H22FN7O.0.4H2O requires C, 59.66; H, 5.71; N, 24.35%.

1. customto give a grey-green milky solution
2. stirringwas stirred at 50° C. under nitrogen for 15 min
3. waitAfter 2.5 h
4. temperaturethe mixture was cooled
5. extractionextracted with dichloromethane (2×50 ml)
6. dry with materialThe extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. washFlash column chromatography on silica gel, eluting with 2% methanol-dichloromethane
10. customgave a brown solid that
11. customwas recrystallised from ethyl acetate-diethyl ether