Acetic Anhydride → N-(5-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-yl)acetamide

Temperature

60 °C

To a solution of 5-{(1E)-3-oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-amine (16 mg, 0.05 mmol) and acetic anhydride (6 μL, 0.06 mmol) in THF (2.4 mL) was added NaHCO3 (5.5 mg, 0.065 mmol). The reaction mixture was warmed at 60° C. and stirred for 40 h. LCMS showed that some starting material was remaining. Another portion of acetic anhydride (6 μL) and NaHCO3 (5.5 mg) were added and the mixture was stirred at 60° C. for 24 h. These additions were repeated twice over 48 h. The mixture was then concentrated, partitioned between water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under vacuum to give an oil. The crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH) to give the title compound (2.3 mg, 12%) as a pale yellow solid.

1. stirringthe mixture was stirred at 60° C. for 24 h
2. waitThese additions were repeated twice over 48 h
3. concentrationThe mixture was then concentrated
4. custompartitioned between water and ethyl acetate
5. extractionThe aqueous layer was extracted twice with ethyl acetate
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customto give an oil
11. customThe crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH)

ORD record

ord-a873a3a3e63847f290f09aae548c67b1

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846711B2