反应详情

温度

65 °C

Pd2(dba)3 (0.192 g, 0.209 mmol), biphenyl-2-yl(dicyclohexyl)phosphane (0.073 g, 0.209 mmol), and 6-chloro-3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.02 g, 2.094 mmol) were placed in a microwave vial under nitrogen and dissolved in THF (11 mL) The reaction mixture was degassed for 5 min, LiHMDS (2.51 mL, 2.51 mmol, 1M in THF) was added via syringe and then heated to 65° C. overnight. The mixture was cooled to RT and Pd2(dba)3 (0.096 g, 0.1 mmol), biphenyl-2-yl(dicyclohexyl)phosphane (0.036 g, 0.1 mmol) and LiHMDS (1.25 mL, 1.25 mmol, 1M in THF) were added again. The mixture was degassed for 5 min and heated to 80° C. for 3 h, cooled to RT and quenched with 1N HCl. The mixture was then concentrated and partitioned between DCM and 1N NaOH. The organic layer was extracted with DCM (3×) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was purified by chromatography on silica gel over a gradient of 0-100% EtOAc in hexanes and then over a gradient of 0-30% (1:2=MeOH:EtOAc) in DCM to yield 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (549 mg, 2.09 mmol, 56%) as a solid. MS ESI calc'd. for C31H26N5 [M+1]+468, found 468.

1. customwas degassed for 5 min
2. temperatureThe mixture was cooled to RT
3. customThe mixture was degassed for 5 min
4. temperatureheated to 80° C. for 3 h
5. temperaturecooled to RT
6. customquenched with 1N HCl
7. concentrationThe mixture was then concentrated
8. custompartitioned between DCM and 1N NaOH
9. extractionThe organic layer was extracted with DCM (3×)
10. dry with materialthe combined organic layers were dried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customThe residue was purified by chromatography on silica gel over a gradient of 0-100% EtOAc in hexanes