Methyl iodide → (+/-)-10-Methyl-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-alpha]azepin-4-one

Temperatur

-78 °C

To a solution of 26.1 g (107.73 mmol) of 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one in dry tetrahydrofuran (450 mL) under argon at −78° C. was added 82.5 mL (82.5 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −78° C. for 10 min and 25.7 mL of methyl iodide (412.7 mmol) was added. The reaction was stirred at −78° C. for 1 h and then at 0° C. for 2 h. The mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1 to afford 11.0 g (40%) of the desired compound as a white solid.

1. stirringThe reaction was stirred at −78° C. for 1 h
2. waitat 0° C. for 2 h
3. customThe mixture was quenched with the addition of a saturated solution of ammonium chloride
4. extractionextracted with ethyl acetate
5. dry with materialThe organic phase was dried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1

ORD-Eintrag

ord-c977c7ef0fe04e3a9c3fce4e64e948a2

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08198287B2