Reaction Steps
To a solution of 2,4-dimethyl-6-oxo-6H-pyran-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide (419 mg, 1.27 mmol) in ethanol (4.0 mL, 70 mmol) were added hydrazine hydrate (370 uL, 7.6 mmol) and acetic acid (4.0 mL, 70 mmol). The mixture was heated at 80° C. for 24 hrs. More hydrazine hydrate (371 uL, 7.63 mmol) was added and stirring continued for 7 hrs. The reaction mixture was adjusted to neutral pH by addition of aq. Sat. Na2CO3. The crude mixture was extracted with dichloromethane (4×40 mL), combined organic phases were washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash chromatography to give the title compound, yield 33%. LC-MS (m/z) 344.4 (MH+); tR=1.32 (method C). 1H NMR (600 MHz, CDCl3): 7.84 (d, J=8.6 Hz, 1H), 7.34 (td, J=7.9, 6.0 Hz, 1H), 7.20 (d, J=7.7 Hz, 1H), 7.17-7.11 (m, 1H), 6.99 (td, J=8.3, 2.0 Hz, 1H), 6.02 (s, 1H), 5.22 (s, 2H), 5.11-5.02 (m, 1H), 2.87-2.75 (m, 1H), 2.29 (s, 3H), 2.24 (m, 1H), 2.05 (s, 3H), 2.00-1.75 (m, 5H). 13C NMR (151 MHz, CDCl3) 166.34, 162.14, 159.96, 146.98, 143.64, 142.71, 130.10 (d, J=8.2 Hz, 1C), 122.78, 118.63, 114.34 (d, J=21.0 Hz, 1C), 114.14, 113.79 (d, J=21.6 Hz, 1C), 58.74, 40.05, 26.17, 25.59, 19.48, 17.49, 16.63.
