反应详情

A mixture of 4-chloro-2-(2,6-dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridine (0.148 g, 0.416 mmol), 6-methylpyrimidin-4-ylamine (0.044 g, 0.458 mmol), XantPhos (0.024 g, 0.0416 mmol), Cs2CO3 (0.271 g, 0.832 mmol) and Pd2(dba)3 (0.019 g, 0.021 mmol) in dioxane (1 mL) was degassed with a stream of argon and was then irradiated at 150° C. for 0.5 hour in a microwave reactor. After cooling to room temperature, the crude reaction mixture was filtered through Celite® washing with DCM and the filtrate was concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-2% MeOH in DCM followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 30 minute gradient 50-90%, 0.1% HCO2H in MeOH/H2O) to afford the title compound (7 mg, 4% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.63 (s, 1H), 8.63 (d, J=1.2 Hz, 1H), 8.45 (d, J=5.6 Hz, 1H), 7.82 (d, J=5.6 Hz, 1H), 7.62 (s, 1H), 7.45 (s, 2H), 2.40 (s, 3H), 2.14-2.05 (m, 1H), 1.13-1.07 (m, 2H), 0.94-0.89 (m, 2H). LCMS (Method C): RT=4.17 min, m/z: 428 [M+H+].

1. customwas degassed with a stream of argon
2. customwas then irradiated at 150° C. for 0.5 hour in a microwave reactor
3. customthe crude reaction mixture
4. filtrationwas filtered through Celite®
5. washwashing with DCM
6. concentrationthe filtrate was concentrated under reduced pressure
7. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-2% MeOH in DCM
8. customC18 on a 30 minute gradient 50-90%, 0.1% HCO2H in MeOH/H2O