Ammonia → 1-(6-(4-Nitronaphthalen-1-yloxy)pyrimidin-4-yl)urea

Temperature

55 °C

To a solution of prop-1-en-2-yl 6-(4-nitronaphthalen-1-yloxy)pyrimidin-4-ylcarbamate (109 mg, 0.298 mmol) and 4-methylmorpholine (3.3 μL, 0.030 mmol) in dry THF (27 mL) was added a solution of NH3 in MeOH (0.6 mL, 1M, 0.6 mmol) and the reaction mixture heated to 55° C. Further aliquots of the methanolic NH3 solution were added after 1 hr (0.6 ml, 0.6 mmol) and after 5 hr (1.0 mL, 1 mmol) and after a further 16 hr the reaction mixture was evaporated in vacuo. The residue was taken up into THF (3.0 mL) and NMM (3.3 μL, 0.030 mmol) and NH3 in MeOH (0.6 mL, 1M, 0.6 mmol) were added and the reaction mixture was heated to 55° C. Further aliquots of the methanolic NH3 solution (1M, 1.0 mL, 1.0 mmol) were added after 2 hr and after 3 hr. After 3.5 hr additional aliquots of NMM (3.3 μL, 0.030 mmol) and methanolic NH3 (1M, 1.0 mL, 1.0 mmol) were added and the reaction mixture was maintained at 55° C. for 15 hr. The reaction mixture was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 4 g, EtOAc in isohexane, 0-100%, gradient elution) to afford the title compound as a yellow solid (60 mg, 61%); Rt 1.87 min (Method 2); m/z 326 (M+H)+ (ES+).

1. customafter a further 16 hr the reaction mixture was evaporated in vacuo
2. additionwere added
3. temperaturethe reaction mixture was heated to 55° C
4. temperaturethe reaction mixture was maintained at 55° C. for 15 hr
5. customThe reaction mixture was evaporated in vacuo
6. customthe residue was purified by flash column chromatography (SiO2, 4 g, EtOAc in isohexane, 0-100%, gradient elution)

ORD record

ord-30792c537f9e424b86b02eb6cbc0335c

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299074B2