Sodium hydride → N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]4-(tert-pentyl)benzenesulfonamide

HRID 1062721Notes

Reaction equation

HRID 1062721 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]([C:27]([CH2:30][CH3:31])([CH3:29])[CH3:28])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[N:7]([CH3:32])[N:6]=1.[H-].[Na+].CC(N(C)C)=O.[Br:41][C:42]1[CH:43]=[N:44][C:45](Cl)=[N:46][CH:47]=1>O1CCCC1.O>[Br:41][C:42]1[CH:43]=[N:44][C:45]([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:22]=[CH:23][C:24]([C:27]([CH2:30][CH3:31])([CH3:28])[CH3:29])=[CH:25][CH:26]=3)(=[O:19])=[O:20])[N:7]([CH3:32])[N:6]=2)=[N:46][CH:47]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 6066655-Bromo-2-chloropyrimidineHCID 22281988N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]4-(tert-pentyl)benzenesulfonamide

Product 1

HCID 9809123N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]4-(tert-pentyl)benzenesulfonamideYield 80.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-4-(tert-pentyl)benzenesulfonamide (Example 8) (270 mg) in tetrahydrofuran (4 ml) at room temperature under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 50 mg) and the mixture was stirred for 1 minute. To the mixture was added dimethyl acetamide (0.5 ml) followed by 5-bromo-2-chloropyrimidine (171 mg) The mixture was stirred for 2 hours at room temperature and then diluted with water (20 ml) and extracted with ether (2×20 ml). The organic fractions were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (35 g) eluted with hexane:ethyl acetate (2:1 to 1:2) to yield the title compound as an orange oil (292 mg).

Workup

  1. stirringwas stirred for 2 hours at room temperature
  2. extractionextracted with ether (2×20 ml)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica (35 g)
  7. washeluted with hexane:ethyl acetate (2:1 to 1:2)

Sources & evidence

ORD record
ord-025052e41e734b78b69f60636c279ca8
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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