تفاعل #531830

معادلة التفاعل

methanesulfonyl chloride

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

carboxylic acid

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

triethylamine

2-amino-3-chloro-5-iodobenzoic acid

triethylamine

methanesulfonyl chloride

→

title compound

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

المذيبات

acetonitrile

acetonitrile

water

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for an additional 5 minutes
3. 3
   أخرىthe temperature below 5° C
4. 4
   workup.STIRRINGThe reaction mixture was stirred 40 minutes at 0° C.
5. 5
   درجة الحرارةThe reaction mixture was then warmed to room temperature
6. 6
   workup.STIRRINGstirred overnight
7. 7
   استخلاصextracted with ethyl acetate (3×50 mL)
8. 8
   غسيلThe combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
9. 9
   تجفيفdried (MgSO4)
10. 10
    تركيزconcentrated under reduced pressure
11. 11
    أخرىThe residual solid was purified by chromatography on silica gel

الإجراء التجريبي

To a solution of methanesulfonyl chloride (0.31 mL, 4.07 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the carboxylic acid product of Example 3, Step D) (1.0 g, 3.87 mmol) and triethylamine (0.54 mL, 3.87 mmol) in acetonitrile (5 mL) at 0° C. The reaction mixture was then stirred for 15 minutes at 0° C. Then, 2-amino-3-chloro-5-iodobenzoic acid (i.e. the product from Step A) (1.15 g, 3.87 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (1.08 mL, 7.74 mmol) in acetonitrile (5 mL) was then added dropwise while keeping the temperature below 5° C. The reaction mixture was stirred 40 minutes at 0° C., and then methanesulfonyl chloride (0.31 mL, 4.07 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL), dried (MgSO4) and concentrated under reduced pressure. The residual solid was purified by chromatography on silica gel to afford 575 mg of the title compound as a crude yellow solid.

المصدر