Reaktion #1265876

Reaktionsgleichung

3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

6-cyano-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

3-picoline

methanesulfonyl chloride

→

title product

Ausbeute 82.0%

2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazin-4-one

Ausbeute 82.0%

Lösungsmittel

water

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was heated to 50° C. for 4 hours
2. 2
   TemperaturThe reaction mixture was then cooled to room temperature
3. 3
   FiltrationThe mixture was filtered
4. 4
   Waschenthe solids were washed sequentially with 4:1 acetonitrile-water (2×2 mL) and acetonitrile (3×2 mL)
5. 5
   Sonstigedried under nitrogen

Vorschrift

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.

Quelle