تفاعل #1265874

معادلة التفاعل

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

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title product

المردود 86.7%

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

المردود 86.7%

المذيبات

water

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىA slurry formed during the addition
2. 2
   غسيلwas rinsed with acetonitrile (10 mL)
3. 3
   workup.STIRRINGAfter stirring for 15 minutes at −5 to 0° C.
4. 4
   درجة الحرارةthe reaction mixture was heated to 50° C.
5. 5
   workup.STIRRINGstirred 4 hours
6. 6
   درجة الحرارةThen the reaction mixture was cooled to room temperature
7. 7
   workup.STIRRINGthe mixture was stirred 15 minutes
8. 8
   ترشيحThe mixture was filtered
9. 9
   أخرىdried under nitrogen

الإجراء التجريبي

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).

المصدر