反应详情

温度

100 °C

A solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (50.0 mg, 0.149 mmol), N-(tert-butyl)-2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (89.0 mg, 0.223 mmol), K2CO3 (62.0 mg, 0.447 mmol) in 1,4-dioxane (20 mL) and water (6 mL) was purged with nitrogen gas for 10 min. PdCl2(dppf)-CH2Cl2 (6.08 mg, 7.45 mol) was added and the reaction mixture purged with nitrogen gas for further 5 min then heated to 100° C. for 12 h. The cooled reaction mixture was filtered through the CELITE® and washed with ethyl acetate (20 mL). The filtrate was washed with brine solution (10 mL). The organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure to give a residue that was purified by preparative HPLC (Condition B-91 as described in general methods) to give N-(tert-butyl)-2-isopropoxy-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (13.0 mg, 15.1%) as a pale yellow solid. LCMS Condition B-79: retention time 2.39 min, [M+1]=572.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15 (s, 9H), 1.41 (d, J=6.5 Hz, 6H), 4.88 (d, J=5.0 Hz, 2H), 5.13 (quintet, J=6.7 Hz, 1H), 6.78 (d, J=2.5 Hz, 1H), 6.89 (s, 1H), 7.28 (t, J=5.5 Hz, 2H), 7.42-7.49 (m, 2H), 7.50-7.62 (m, 4H), 7.74-7.81 (m, 1H), 7.92 (d, J=2.5 Hz, 1H), 8.40-8.45 (m, 1H), 8.66 (d, J=2.5 Hz, 1H), 8.75 (d, J=2.5 Hz, 1H).

1. customthe reaction mixture purged with nitrogen gas for further 5 min
2. customThe cooled reaction mixture
3. filtrationwas filtered through the CELITE®
4. washwashed with ethyl acetate (20 mL)
5. washThe filtrate was washed with brine solution (10 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. customevaporated under reduced pressure
9. customto give a residue that
10. customwas purified by preparative HPLC (Condition B-91 as described in general methods)