Reaktion #531821

Reaktionsgleichung

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

Lösungsmittel

acetonitrile

acetonitrile

water

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for an additional 5 minutes
3. 3
   Sonstigethe temperature below 5° C
4. 4
   workup.STIRRINGThe reaction mixture was stirred 40 minutes at 0° C.
5. 5
   TemperaturThe reaction mixture was then warmed to room temperature
6. 6
   workup.STIRRINGstirred overnight
7. 7
   Extraktionextracted with ethyl acetate (3×50 mL)
8. 8
   WaschenThe combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
9. 9
   Trocknendried (MgSO4)
10. 10
    Einengenconcentrated

Vorschrift

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.

Quelle