反応 #531821

反応方程式

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-methyl-5-iodobenzoic acid

triethylamine

methanesulfonyl chloride

→

title product

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

溶媒

acetonitrile

acetonitrile

water

acetonitrile

反応条件

後処理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for an additional 5 minutes
3. 3
   その他the temperature below 5° C
4. 4
   workup.STIRRINGThe reaction mixture was stirred 40 minutes at 0° C.
5. 5
   温度The reaction mixture was then warmed to room temperature
6. 6
   workup.STIRRINGstirred overnight
7. 7
   抽出extracted with ethyl acetate (3×50 mL)
8. 8
   洗浄The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
9. 9
   乾燥dried (MgSO4)
10. 10
    濃縮concentrated

実験手順

To a solution of methanesulfonyl chloride (0.63 mL, 8.13 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 Step D) (2.0 g, 7.75 mmol) and triethylamine (1.08 ml, 7.75 mmol) in acetonitrile (5 mL) at 0° C. The reaction mixture was then stirred for 15 minutes at 0° C. Then, 2-amino-3-methyl-5-iodobenzoic acid (i.e. the product from Example 1, Step A) (2.14 g, 7.75 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (2.17 mL, 15.15 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 (0.63 mL, 8.13 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 to afford 3.18 g of the title product as a crude yellow solid.

出典