Sodium hydride → HCID 22281951, compound

HRID 1368628Notes

Reaction equation

HRID 1368628 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[C:16]=2[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[CH:26]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:34][C:35]1[CH:36]=[N:37][C:38](Cl)=[N:39][CH:40]=1.[Cl-].[NH4+]>O1CCCC1.CN(C)C(=O)C.O>[Br:34][C:35]1[CH:36]=[N:37][C:38]([O:24][CH2:23][CH2:22][O:21][C:17]2[C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[CH:26]=3)=[C:15]([NH:14][S:11]([C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:10][CH:9]=3)(=[O:13])=[O:12])[N:19]([CH3:20])[N:18]=2)=[N:39][CH:40]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 6066655-Bromo-2-chloropyrimidineHCID 22282023HCID 22282023, compound

Product 1

HCID 22281951HCID 22281951, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To 4-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(3-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (Preparation 61) (101 mg) in tetrahydrofuran (2 ml) and N,N-dimethylacetamide (0.5 ml) at 0° C. was added sodium hydride (20 mg of a 60% dispersion in oil) followed by the 5-bromo-2-chloropyrimidine (66 mg) The reaction was stirred for one hour at 0° C. and then at room temperature overnight. Water (3 ml) was then added to the reaction followed by saturated aqueous ammonium chloride (3 ml) and the mixture was extracted with ethyl acetate (3×5 mls). The combined organics were then washed with 1:1 saturated ammonium chloride and water (4×15 ml) and dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield the crude material (130 mg). The crude material was purified by HPLC on a 5μ ODS Phenomenex Magellen™ column with a gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%) to yield the desired product as an off white solid (12 mg).

Workup

  1. customat room temperature
  2. customovernight
  3. extractionthe mixture was extracted with ethyl acetate (3×5 mls)
  4. washThe combined organics were then washed with 1:1 saturated ammonium chloride and water (4×15 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto yield the crude material (130 mg)
  9. customThe crude material was purified by HPLC on a 5μ ODS Phenomenex Magellen™ column with a gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%)

Sources & evidence

ORD record
ord-1f47c01250cb4b5c966b0dab625dc70b
Source dataset
uspto-grants-2003_06
Patent number
US06573270B1

Reaction notes

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