Water → Tert-butyl 4-(((2-chloro-5-iodopyridin-4-yl)amino)methyl)piperidine-1-carboxylate

NaH (0.098 g, 3.9 mmol) was added to a solution of 2-chloro-5-iodopyridin-4-amine (0.500 g, 1.96 mmol) in DMF (12 mL) and the mixture was stirred for 30 min at r.t. The temperature was then raised to 80° C. and a solution of tert-butyl 4-(bromomethyl)-piperidine-1-carboxylate (1.093 g, 3.93 mmol) in DMF (2 mL) was added. The reaction mixture was stirred at 80° C. for 2 h, then cooled to r.t. NaH (0.050 g, 2.00 mmol) was added and the reaction mixture was heated for 1 h at 80° C. After cooling, water (40 mL) was added and the reaction mixture was partitioned between ethyl acetate and aq. NaHCO3. The organic phase was washed with brine, dried (MgSO4) and concentrated. The crude product was purified by flash silica chromatography, eluting with ethyl acetate and hexane (1/9), to give the title compound as a pink solid (0.405 g, 46%).

1. temperatureThe temperature was then raised to 80° C.
2. stirringThe reaction mixture was stirred at 80° C. for 2 h
3. temperaturecooled to r.t
4. temperaturethe reaction mixture was heated for 1 h at 80° C
5. temperatureAfter cooling
6. customthe reaction mixture was partitioned between ethyl acetate and aq. NaHCO3
7. washThe organic phase was washed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customThe crude product was purified by flash silica chromatography
11. washeluting with ethyl acetate and hexane (1/9)

ORD record

ord-5aab0959a2f846f08f0d22d5f2ad4fc3

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08058045B2