Citric Acid → N-[3-{2-[(5-chloropyrimidin-2-yl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamide

HRID 1062741Notes

Reaction equation

HRID 1062741 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[C:8]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:28])[N:6]=1.[H-].[Na+].[Cl:31][C:32]1[CH:33]=[N:34][C:35](S(C)(=O)=O)=[N:36][CH:37]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Cl:31][C:32]1[CH:33]=[N:34][C:35]([O:1][CH2:2][CH2:3][O:4][C:5]2[C:9]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)=[C:8]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=3)(=[O:19])=[O:20])[N:7]([CH3:28])[N:6]=2)=[N:36][CH:37]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydride2×HCID 27277255-Chloro-2-methanesulfonylpyrimidine2×HCID 22281909N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamide

Product 1

HCID 22282045N-[3-{2-[(5-chloropyrimidin-2-yl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamideYield 78.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-2-pyridine sulphonamide (Example 50) (100 mg) in dry tetrahydrofuran (5 ml) at room temperature was added sodium hydride (80% dispersion in oil, 20 mg) the mixture was stirred for 20 minutes. A solution of 5-chloro-2-methylsulphonylpyrimidine (72 mg) in dry tetrahydrofuran (2.5 ml) was then added and the mixture was stirred for a further 16 hours. The mixture was then treated with further sodium hydride (80% dispersion in oil, 20 mg) and after 15 minutes stirring further 5-chloro-2-methylsulphonylpyrimidine (84 mg) was also added. The mixture was stirred for 4 hours. The reaction was treated with citric acid (10% aq.) and extracted with ethyl acetate (50 ml). The organic fraction was washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (10 g) eluted with a solvent gradient of pentane:ethyl acetate (8:2 to 0:1) to yield the tile compound as a yellow solid (101 mg).

Workup

  1. stirringthe mixture was stirred for a further 16 hours
  2. additionwas also added
  3. stirringThe mixture was stirred for 4 hours
  4. extractionextracted with ethyl acetate (50 ml)
  5. washThe organic fraction was washed with brine (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica (10 g)
  10. washeluted with a solvent gradient of pentane:ethyl acetate (8:2 to 0:1)

Sources & evidence

ORD record
ord-f7b3b8e2dd2742a0b63074b8c95802fe
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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