Acetic Acid → 10-Azido-10-methyl-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

Temperature

-78 °C

To a solution of 10.0 g (39.0 mmol) (+/−)10-methyl-2-pyrimidin -4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one in a mixture of dry tetrahydrofuran/dimethyltetrahydropyrimidinone (150/20 mL) under argon at −78° C. was added 81.9 mL (81.9 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −78° C. for 5 min. The solution was warmed to 0° C. by changing the cold bath and 13.3 g (42.9 mmol) of 2,4,6-triisopropylbenzene -sulfonyl azide in 30 mL of dry tetrahydrofuran was added. The reaction was stirred at 0° C. for 1 h, at room temperature for 1 h and 10.0 mL (175.6 mmol) of acetic acid was added. The mixture was stirred at room temperature for 1 h and then diluted with ethyl acetate. The organic phase was washed with water and a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to afford 10-azido-1 0-methyl-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one as an orange oil. The compound was used as such in the next step.

1. temperatureThe solution was warmed to 0° C.
2. additionwas added
3. stirringThe reaction was stirred at 0° C. for 1 h, at room temperature for 1 h
4. stirringThe mixture was stirred at room temperature for 1 h
5. washThe organic phase was washed with water
6. dry with materiala saturated solution of sodium chloride, dried over sodium sulfate
7. concentrationconcentrated

ORD record

ord-e268f558d80340b0bb8fe8e0d71926c4

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198287B2