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 10.00 g (41.27 mmol) of 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one in dry tetrahydrofuran (200 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 purified by flash chromatography (dichloromethane with 1% of methanol) to afford 11.0 g of a white solid (40%).

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 purified by flash chromatography (dichloromethane with 1% of methanol)

ORD-Eintrag

ord-14918eeb74f84788a169e02e4755dfc6

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08614219B2