1-Methylimidazole → HCID 82895561, compound

Temperature

-78 °C

n-BuLi (1.6 M in hexane, 3.71 mL, 5.94 mmol) was added to a solution of 1-methylimidazole (0.452 mL, 5.7 mmol) in THF (10 mL) at −78° C. The mixture was stirred at −78° C. for 30 min. Chlorotriethylsilane (0.957 mL, 5.7 mmol) was added slowly. The mixture was stirred at −78° C. for 30 min. A second portion of n-BuLi (1.6 M in hexane, 3.71 mL, 5.94 mmol) was added. The mixture was stirred at −78° C. for 30 min. Crude N-methoxy-N-methylpyrimidine-5-carboxamide (794 mg, 4.75 mmol, Intermediate 28, step a) was added via cannula as a solution in THF (5 mL). The mixture was stirred at −78° C. for 5 min and was removed from the cold bath and stirred at room temperature overnight. Saturated aqueous NH4Cl was added and the phases were separated. The aqueous phase was extracted twice with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 10-100% EtOAc-heptanes, then 0-10% MeOH-EtOAc) to afford impure title compound, which was further purified by flash column chromatography (silica gel, 4-5% MeOH-DCM).

1. stirringThe mixture was stirred at −78° C. for 30 min
2. stirringThe mixture was stirred at −78° C. for 30 min
3. stirringThe mixture was stirred at −78° C. for 5 min
4. customwas removed from the cold bath
5. stirringstirred at room temperature overnight
6. additionSaturated aqueous NH4Cl was added
7. customthe phases were separated
8. extractionThe aqueous phase was extracted twice with DCM
9. dry with materialThe organic phase was dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by flash column chromatography (silica gel, gradient 10-100% EtOAc-heptanes

ORD record

ord-242ea66578c14de7a36bcbe831767051

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2