Reaktion #1265874

Reaktionsgleichung

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

methanesulfonyl chloride

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

3-picoline

3-picoline

→

title product

Ausbeute 86.7%

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

Ausbeute 86.7%

Lösungsmittel

water

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA slurry formed during the addition
2. 2
   Waschenwas rinsed with acetonitrile (10 mL)
3. 3
   workup.STIRRINGAfter stirring for 15 minutes at −5 to 0° C.
4. 4
   Temperaturthe reaction mixture was heated to 50° C.
5. 5
   workup.STIRRINGstirred 4 hours
6. 6
   TemperaturThen the reaction mixture was cooled to room temperature
7. 7
   workup.STIRRINGthe mixture was stirred 15 minutes
8. 8
   FiltrationThe mixture was filtered
9. 9
   Sonstigedried under nitrogen

Vorschrift

To a solution of methanesulfonyl chloride (5.0 mL, 7.4 g, 65 mmol) in acetonitrile (55 mL) at −5° C. was added dropwise a solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (see WO 03/015519 for preparation) (93.6% purity, 16.16 g, 50.0 mmol) and 3-picoline (8.3 mL, 7.9 g, 85 mmol) in acetonitrile (50 mL) over five minutes while maintaining the temperature at about −5 to 0° C. A slurry formed during the addition. The mixture was stirred for 5 minutes at this temperature, and then 6-chloro-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (99.0% purity, 11.22 g, 52.5 mmol) was added all at once, and the residue was rinsed with acetonitrile (10 mL). To the reaction mixture was added 3-picoline (8.3 mL, 7.9 g, 85 mmol) dropwise in 5 minutes at −5 to 0° C. After stirring for 15 minutes at −5 to 0° C., the reaction mixture was heated to 50° C. and stirred 4 hours. Then the reaction mixture was cooled to room temperature, water (30 mL) was added dropwise and the mixture was stirred 15 minutes. The mixture was filtered, and the solids were re-slurried sequentially with 4:1 acetonitrile-water (2×40 mL) and acetonitrile (3×40 mL), and then dried under nitrogen to afford the title product as a light yellow powder, 20.95 g (93.6% purity by HPLC, 86.7% yield calculated based on the purity).

Quelle