反应详情

Sodium hydride (55.2 mg, 1.379 mmol) was added to a solution of 7-iodo-1H-pyrazolo[4,3-b]pyridine (260 mg, 1.061 mmol) in DMF (1.5 mL) at 0° C., and the reaction was stirred for 5 minutes. tert-Butyl 4-bromopiperidine-1-carboxylate (364 mg, 1.379 mmol) was added and the reaction was warmed to room temperature and then heated at 65° C. for 2 hours. The reaction was cooled, quenched with water, and concentrated in vacuo. The residue was partitioned between saturated NH4Cl solution and EtOAc. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo to afford a residue. The residue was purified with silica column chromatography eluted with hexanes/ethyl acetate step gradient (0-100% EtOAc over 45 minutes), to afford tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylate (57 mg, 13%). The fractions containing tert-butyl 4-(7-iodo-1H-pyrazolo[4,3-b]pyridin-1-yl)piperidine-1-carboxylate were chromatographed again under the same conditions to give tert-butyl 4-(7-iodo-1H-pyrazolo[4,3-b]pyridin-1-yl)piperidine-1-carboxylate (60 mg, 13%). MS [M+H] found 429.2

1. temperatureheated at 65° C. for 2 hours
2. temperatureThe reaction was cooled
3. customquenched with water
4. concentrationconcentrated in vacuo
5. customThe residue was partitioned between saturated NH4Cl solution and EtOAc
6. customThe organic layer was separated
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customto afford a residue
10. customThe residue was purified with silica column chromatography
11. washeluted with hexanes/ethyl acetate step gradient (0-100% EtOAc over 45 minutes)