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

HRID 1062728Notes

Reaction equation

HRID 1062728 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]([CH3:31])=[CH:27][CH:26]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:35]1[N:40]=[CH:39][C:38]([S:41][CH3:42])=[CH:37][N:36]=1.[Cl-].[NH4+]>O1CCCC1.CC(N(C)C)=O.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][O:24][C:35]3[N:40]=[CH:39][C:38]([S:41][CH3:42])=[CH:37][N:36]=3)[C:16]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 219795322-Chloro-5-(methylthio)pyrimidineHCID 222820434-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

Product 1

HCID 99596764-(tert-butyl)-N-[3-{2-[(5-methylthio-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamideYield 96.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To 4-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (Example 2, 743 mg) in tetrahydrofuran (25 ml) at 0° C. under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 141 mg), the reaction mixture was stirred for 5 minutes. A solution of 2-chloro-5-(methylthio)pyrimidine (269 mg) in dimethyl acetamide (5 ml) was added and the reaction mixture allowed to warm up to room temperature. The reaction mixture was stirred for a further 2 hours. The reaction mixture was poured cautiously into a stirred bi-phasic solution of saturated aqueous ammonium chloride solution (100 ml) and ethyl acetate (100 ml). The organic fraction was separated, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (140 g) eluted with ethyl acetate:hexane (1:1) to yield the title compound as a yellow oil (921 mg).

Workup

  1. stirringThe reaction mixture was stirred for a further 2 hours
  2. customThe organic fraction was separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica (140 g)
  7. washeluted with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-2818f0fbd5e4490096613db3417fb160
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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