反应详情

温度

100 °C

In a 250 mL round-bottomed flask, tert-butyl 6-(6-aminopyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (870 mg, 3.00 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (670 mg, 3.00 mmol), xantphos (260 mg, 449 μmol), Cs2CO3 (2.93 g, 8.99 mmol) and Pd2(dba)3 (137 mg, 150 μmol) were combined with dioxane (25.0 ml) to give a dark brown solution. The reaction mixture was heated to 100° C. under argon and stirred for 20 h. The reaction was cooled to 25° C., diluted with DCM, and Na2SO4 was added. The mixture was filtered over celite, the filter cake was washed with DCM and the filtrate was conc. in vacuo to a dark brown semisolid. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 5% MeOH in DCM). The impure material was repurified by flash chromatography (silica gel, 220 g, 0% to 4% MeOH in DCM) to afford 0.320 g (25%) of the title compound as a light yellow powder. (M+H)+=433/435 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.12 (s, 1H), 8.08 (s, 1H), 7.65 (s, 1H), 6.82 (d, J=1.5 Hz, 2H), 4.12 (s, 4H), 4.01 (s, 3H), 3.80 (s, 4H), 1.45 (s, 9H).

1. customto give a dark brown solution
2. temperatureThe reaction was cooled to 25° C.
3. additionwas added
4. filtrationThe mixture was filtered over celite
5. washthe filter cake was washed with DCM
6. customThe crude material was purified by flash chromatography (silica gel, 220 g, 0% to 5% MeOH in DCM)
7. customThe impure material was repurified by flash chromatography (silica gel, 220 g, 0% to 4% MeOH in DCM)