반응 #992703

반응 방정식

3-picoline

3-picoline

methanesulfonyl chloride

methanesulfonyl chloride

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

5-chloro-7-methylindoline-2,3-dione

→

title compound

2-[[[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]carbonyl]amino]-5-chloro-3-methyl-α-oxobenzeneacetic acid

3-picoline

용매

water

acetonitrile

반응 조건

후처리

1. 1
   온도the mixture was warmed to room temperature for 2 hours
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at room temperature for 3 hours
4. 4
   온도The mixture was cooled to 0° C.
5. 5
   workup.STIRRINGstirring at 0-5° C.
6. 6
   workup.WAITwas continued for 1 hour
7. 7
   여과Then the mixture was filtered
8. 8
   세척the solids were washed with 2:1 acetonitrile-water (3×3 mL)
9. 9
   기타dried under nitrogen

실험 절차

To a suspension of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (see PCT Patent Publication WO 03/015519 for preparation) (97.6% purity, 3.25 g, 10.5 mmol) and 5-chloro-7-methylindoline-2,3-dione (K. Tsuji et al., Bioorg. Med. Chem. Letters, 2002, 12(17), pp 2427-2430) (1.96 g, 10.0 mmol) in dry acetonitrile (12 mL) was added 3-picoline (2.60 g, 28 mmol). The mixture was cooled to 0° C., and then methanesulfonyl chloride (1.48 g, 12.9 mmol) was added dropwise at 0-10° C. After stirring 5 minutes at this temperature, the mixture was warmed to room temperature for 2 hours. Then additional quantities of 3-picoline (0.37 g, 4.0 mmol) and methanesulfonyl chloride (0.24 g, 2.1 mmol) were added, and stirring was continued at room temperature for 3 hours. The mixture was cooled to 0° C., water (6 mL) was added dropwise, and stirring at 0-5° C. was continued for 1 hour. Then the mixture was filtered, and the solids were washed with 2:1 acetonitrile-water (3×3 mL), and dried under nitrogen to afford the 3-picoline salt of the title compound as a light green solid, 1.23 g.

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