3-Methylpyridine → 3-Methylpyridine

HRID 905521Notes

Reaction equation

HRID 905521 reaction equation
[Br:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1.[Cl:17][C:18]1[CH:19]=[C:20]2[C:24](=[C:25]([CH3:27])[CH:26]=1)[NH:23][C:22](=[O:28])[C:21]2=[O:29].N1C=CC=C(C)C=1.CS(Cl)(=O)=[O:39]>C(#N)C.O>[N:23]1[CH:22]=[CH:21][CH:27]=[C:25]([CH3:26])[CH:24]=1.[Br:1][C:2]1[CH:6]=[C:5]([C:7]([NH:23][C:24]2[C:25]([CH3:27])=[CH:26][C:18]([Cl:17])=[CH:19][C:20]=2[C:21](=[O:29])[C:22]([OH:39])=[O:28])=[O:9])[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1

Participants

8

Reactant 4

HCID 79703-Methylpyridine2×HCID 31297Methanesulfonyl chloride2×HCID 3667105-Chloro-7-methylisatinHCID 115875353-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid

Product 2

HCID 79703-MethylpyridineHCID 16047911HCID 16047911, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  1. temperaturethe mixture was warmed to room temperature for 2 hours
  2. stirringstirring
  3. waitwas continued at room temperature for 3 hours
  4. temperatureThe mixture was cooled to 0° C.
  5. stirringstirring at 0-5° C.
  6. waitwas continued for 1 hour
  7. filtrationThen the mixture was filtered
  8. washthe solids were washed with 2:1 acetonitrile-water (3×3 mL)
  9. customdried under nitrogen

Sources & evidence

ORD record
ord-9d6b5acae5dc4b88824382e12fbe6ccc
Source dataset
uspto-grants-2011_09
Patent number
US08012499B2

Reaction notes

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