反应 #531830
ord-e18181eb71b54f078bce9bcb1cda816b
反应方程式
反应物
试剂
反应条件
后处理
- 1workup.STIRRINGstirring
- 2workup.WAITwas continued for an additional 5 minutes
- 3其他the temperature below 5° C
- 4workup.STIRRINGThe reaction mixture was stirred 40 minutes at 0° C.
- 5温度The reaction mixture was then warmed to room temperature
- 6workup.STIRRINGstirred overnight
- 7萃取extracted with ethyl acetate (3×50 mL)
- 8洗涤The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
- 9干燥dried (MgSO4)
- 10浓缩concentrated under reduced pressure
- 11其他The residual solid was purified by chromatography on silica gel
实验过程
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.