Reaction #792163

Reaction equation

2-amino-3-methyl-5-chlorobenzoic acid

2-Amino-3-methyl-5-chlorobenzoic acid

methanesulfonyl chloride

carboxylic acid

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

triethylamine

triethylamine

methanesulfonyl chloride

→

title product

Yield 38.4%

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

Yield 38.4%

Solvents

acetonitrile

acetonitrile

acetonitrile

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for an additional 10 minutes
3. 3
   Otherthe temperature below 10° C
4. 4
   workup.STIRRINGThe reaction mixture was stirred 60 minutes at 0° C.
5. 5
   TemperatureThe reaction mixture was then warmed to room temperature
6. 6
   workup.STIRRINGstirred for an additional 2 hours
7. 7
   ConcentrationThe reaction mixture was then concentrated
8. 8
   Otherthe crude product was chromatographed on silica gel

Procedure

To a solution of methanesulfonyl chloride (6.96 g, 61.06 mmol) in acetonitrile (150 mL) was added dropwise a mixture of the carboxylic acid product from Step D (15.0 g, 58.16 mmol) and triethylamine (5.88 g, 58.16 mmol) in acetonitrile (150 mL) at ˜5° C. The reaction mixture was then stirred for 30 minutes at 0° C. Then, 2-amino-3-methyl-5-chlorobenzoic acid from Example 6, Step A (10.79 g, 58.16 mmol) was added, and stirring was continued for an additional 10 minutes. A solution of triethylamine (11.77 g, 116.5 mmol) in acetonitrile was then added dropwise while keeping the temperature below 10° C. The reaction mixture was stirred 60 minutes at 0° C., and then methanesulfonyl chloride (6.96 g, 61.06 mmol) was added. The reaction mixture was then warmed to room temperature and stirred for an additional 2 hours. The reaction mixture was then concentrated, and the crude product was chromatographed on silica gel using methylene chloride as eluent to afford the title product as a yellow solid (9.1 g).

Source