Sodium hydride → HCID 22281990, compound

HRID 1368586Notes

Reaction equation

HRID 1368586 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)=[C:15]([NH:24][S:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[N:14]([CH3:38])[N:13]=2)=[N:6][CH:7]=1.[H-].[Na+].CC(N(C)C)=O.C([Li])CCC>O1CCCC1>[CH3:38][N:14]1[C:15]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([CH3:36])([CH3:37])[CH3:35])=[CH:30][CH:29]=2)(=[O:27])=[O:26])=[C:16]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:12]([O:11][CH2:10][CH2:9][O:8][C:5]2[N:4]=[CH:3][CH:2]=[CH:7][N:6]=2)=[N:13]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 9894949N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-4-(tert-butyl)benzenesulfonamideHCID 178418339Butyllithium

Product 1

HCID 22281990HCID 22281990, compoundYield 5.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]4-(tert-butyl)benzenesulfonamide (Example 3, 100 mg) in anhydrous tetrahydrofuran (2 ml) at 0° C. under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 18 mg), followed by dimethyl acetamide (0.5 ml). The mixture was cooled to −78° C. and n-butyl lithium (1.6M in hexanes, 0.1 ml) was added dropwise under an atmosphere of nitrogen. The yellow solution was allowed to stir at −78° C. for 20 minutes. 1.25 ml of this solution was withdrawn by syringe and added dropwise to a mixture of ether (10 m) and water (10 ml). The aqueous layer was extracted with ether (3×10 ml). The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (10 g) eluted with ethyl acetate:hexane (2:1) to yield the title compound as a white solid (5 mg).

Workup

  1. custom1.25 ml of this solution was withdrawn by syringe
  2. additionadded dropwise to a mixture of ether (10 m) and water (10 ml)
  3. extractionThe aqueous layer was extracted with ether (3×10 ml)
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica (10 g)
  8. washeluted with ethyl acetate:hexane (2:1)

Sources & evidence

ORD record
ord-e9ea624dfec843b3b08291ebc083fcf7
Source dataset
uspto-grants-2003_06
Patent number
US06573270B1

Reaction notes

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