反应详情

A 48 mL sealed tube was charged with N-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine (0.150 g, 0.439 mmol), 1H-pyrazol-4-ylboronic acid (0.0737 g, 0.658 mmol), and DMF (3.00 ml, 38.6 mmol). A solution of potassium carbonate (0.182 g, 1.32 mmol) and water (0.696 ml, 38.6 mmol) was added, followed by PdCl2(dppf)-CH2Cl2Adduct (0.0358 g, 0.0439 mmol). The tube was flushed with argon, sealed, then placed in a 90° C. oil bath for 5 hours. The mixture was concentrated and the black solid was triturated with water to remove K2CO3, then purified by column chromatography using a 40 g RediSep column, eluting with 30-70% (90:10:1 DCM:MeOH:NH4OH solution) in DCM over 40 minutes. Pure fractions were collected to give N-((6-(1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine as a white solid. MS (ESI pos. ion) m/z: 374 (MH+). Calc'd exact mass for C18H15N9O: 373.

1. customA 48 mL sealed tube
2. customThe tube was flushed with argon
3. customsealed
4. customplaced in a 90° C.
5. customfor 5 hours
6. concentrationThe mixture was concentrated
7. customthe black solid was triturated with water
8. customto remove K2CO3
9. custompurified by column chromatography
10. washeluting with 30-70% (90:10:1 DCM:MeOH:NH4OH solution) in DCM over 40 minutes
11. customPure fractions were collected