Urea → N-(6-Fluoro-1H-indazol-5-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide

Temperature

80 °C

The product of Step (d) (41.0 mg, 0.276 mmol, 1.0 equiv) was dissolved in CH3CN (1 mL) and diketene (0.021 mL, 0.276 mmol, 1.0 equiv) was added. The reaction was heated to 80° C. for 2 hours, then cooled to room temperature and concentrated. The residue was dissolved in CH3CN (1 mL). 4-Fluorobenzaldehyde (0.030 mL, 0.276 mmol, 1.00 equiv), urea (25 mg, 0.41 mmol, 1.5 equiv), and ytterbium triflate (17 mg, 0.028 mmol, 0.10 equiv) and heated to 80° C. for 3 hours. The reaction was cooled to room temperature and water was added. The precipitate was collected by filtration and washed alternately with CH3CN and Et2O. The residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min) to provide 3 mg (3%) of the title compound. MS (ES+) m/e 384 [M+H].

1. temperaturecooled to room temperature
2. concentrationconcentrated
3. dissolutionThe residue was dissolved in CH3CN (1 mL)
4. temperatureThe reaction was cooled to room temperature
5. filtrationThe precipitate was collected by filtration
6. washwashed alternately with CH3CN and Et2O
7. customThe residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min)

ORD record

ord-5511ecf4142c4108b0f328f25724d995

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07560467B2