3-Methylpyridine → 2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]-8-methyl-4-oxo-4H-3,1-benzoxazine-6-carbonitrile

温度

-5 °C

A mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (97.9% purity, 3.09 g, 10.0 mmol), 6-cyano-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (96.3% purity, 2.10 g, 10.0 mmol) and 3-picoline (3.30 mL, 3.16 g, 34 mmol) in acetonitrlle (65 mL) was cooled to about −5° C. Then methanesulfonyl chloride (1.0 mL, 1.5 g, 13 mmol) in acetonitrile (3 mL) was added dropwise at −5 to 0° C. After 15 minutes at −5 to 0° C., the reaction mixture was heated to 50° C. for 4 hours. The reaction mixture was then cooled to room temperature, water (4 mL) was added dropwise, and the reaction mixture was stirred 15 minutes. The mixture was filtered, and the solids were washed sequentially with 4:1 acetonitrile-water (2×2 mL) and acetonitrile (3×2 mL), and dried under nitrogen to afford the title product as a pale green powder, 3.71 g (94.2% purity by HPLC, 82.0% yield calculated based on the purity), melting at 263-267° C.

1. temperaturethe reaction mixture was heated to 50° C. for 4 hours
2. temperatureThe reaction mixture was then cooled to room temperature
3. filtrationThe mixture was filtered
4. washthe solids were washed sequentially with 4:1 acetonitrile-water (2×2 mL) and acetonitrile (3×2 mL)
5. customdried under nitrogen

ORDレコード

ord-f2a6c4c5037c4722b182d69effdff4b3

出典データセット

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07276601B2