Sodium hydride → n-{3-{2-[(5-Bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-[4-(trifluoromethyl)phenyl]-1h-pyrazol-5-yl}-4-(tert-butyl)benzenesulfonamide

HRID 1062722Notes

Reaction equation

HRID 1062722 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][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:37][C:38]1[CH:39]=[N:40][C:41](Cl)=[N:42][CH:43]=1.[Cl-].[NH4+]>C1COCC1.O>[Br:37][C:38]1[CH:39]=[N:40][C:41]([O:24][CH2:23][CH2:22][O:21][C:17]2[C:16]([C:25]3[CH:26]=[CH:27][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:29][CH:30]=3)=[C:15]([NH:14][S:11]([C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:10][CH:9]=3)(=[O:12])=[O:13])[N:19]([CH3:20])[N:18]=2)=[N:42][CH:43]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 6066655-Bromo-2-chloropyrimidineHCID 222819594-(Tert-butyl)-n-{3-(2-hydroxyethoxy)-1-methyl-4-[4-(trifluoromethyl)phenyl]-1h-pyrazol-5-yl}benzenesulfonamide

Product 1

HCID 22281910n-{3-{2-[(5-Bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-[4-(trifluoromethyl)phenyl]-1h-pyrazol-5-yl}-4-(tert-butyl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 4-(tert-butyl)-N-{3-(2-hydroxyethoxy)-1-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl}benzenesulfonamide (Example 12) (60 mg) in THF (6 ml) at 0° C. was added sodium hydride (12 mg of a 60% dispersion in oil) followed by the 5-bromo-2-chloropyrimidine (39 mg) The reaction was stirred for one hour at 0° C. and then at room temperature overnight. Water (5 ml) was then added to the reaction followed by saturated aqueous ammonium chloride (5 ml) and the mixture was extracted with ethyl acetate (3×10 ml). The combined organics were washed with saturated aqueous ammonium chloride (20 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield the crude material (61 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 (15.5 mg).

Workup

  1. customat room temperature
  2. customovernight
  3. extractionthe mixture was extracted with ethyl acetate (3×10 ml)
  4. washThe combined organics were washed with saturated aqueous ammonium chloride (20 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto yield the crude material (61 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-aea5d540cde542969e127959dd422d6e
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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