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

HRID 1062736Notes

Reaction equation

HRID 1062736 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]([CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:30])[N:6]=1.[H-].[Na+].[Br:33][C:34]1[CH:35]=[N:36][C:37](Cl)=[N:38][CH:39]=1>C1COCC1.CC(N(C)C)=O>[Br:33][C:34]1[CH:35]=[N:36][C:37]([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]([CH:27]([CH3:28])[CH3:29])=[CH:23][N:22]=3)(=[O:19])=[O:20])[N:7]([CH3:30])[N:6]=2)=[N:38][CH:39]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 22282040N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

Product 1

HCID 9829887N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamideYield 45.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide (Example 40) (1.00 g) in anhydrous THF (10 ml) at 0° C. and under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 195 mg) and the mixture was stirred for 5 minutes. To the mixture was added 5-bromo-2-chloropyrimidine (Liquid Crystals, 1993, 14(3), 741) (1.12 g) in dimethylacetamide (3 ml). After stirring for 1 hr, the reaction mixture was partitioned between ethyl acetate (100 ml) and saturated ammonium chloride solution (100 ml). The organic fraction was washed with brine (100 ml), followed by drying over magnesium sulfate, filtering and concentration under reduced pressure. Purification of the residue by preparative HPLC on a Phenomenex Magellen column using a 0.1M ammonium acetate acetonitrile gradient (95:5 to 50:50 over 5 minutes) afforded the title compound as a white solid (625 mg).

Workup

  1. stirringAfter stirring for 1 hr
  2. customthe reaction mixture was partitioned between ethyl acetate (100 ml) and saturated ammonium chloride solution (100 ml)
  3. washThe organic fraction was washed with brine (100 ml)
  4. dry with materialby drying over magnesium sulfate
  5. filtrationfiltering
  6. concentrationconcentration under reduced pressure
  7. customPurification of the residue by preparative HPLC on a Phenomenex Magellen column
  8. customa 0.1M ammonium acetate acetonitrile gradient (95:5 to 50:50 over 5 minutes)

Sources & evidence

ORD record
ord-8f3e7202d8b14b90ac90391704f79708
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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