Potassium Carbonate → N'-[5-[4-(2-hydroxyethoxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylurea

HRID 351249Notes

Reaction equation

HRID 351249 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[N:11]=[C:10]([NH:21][C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[CH:9]=2)=[CH:4][CH:3]=1.[Si]([O:34][CH2:35][CH2:36]Br)(C(C)(C)C)(C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[OH:34][CH2:35][CH2:36][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[N:11]=[C:10]([NH:21][C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[CH:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane2×HCID 135737387N'-[5-(4-hydroxyphenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylurea

Product 1

HCID 21091146N'-[5-[4-(2-hydroxyethoxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylureaYield 83.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of N′-[5-[4-(hydroxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylurea (121.9 mg), 2-(tert-butyl-dimethylsilyloxy)ethyl bromide (166 mg), and K2CO3 (95.6 mg) in DMF (1.5 ml) was stirred at 75° C. for 7 hours. 2-(tert-butyldimethylsilyloxy)ethyl bromide (83 mg) and KI (57.4 mg) was added to the reaction mixture, and the mixture was stirred at 75° C. overnight. The mixture was allowed to cool to ambient temperature, and was partitioned between ethyl acetate and H2O. The aqueous layer was reextracted with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by 5% MeOH/CHCl3. The separated silica gel was extracted with 10% MeOH/CHCl3 and the solvent was evaporated in vacuo to give N′-[5-[4-(2-hydroxyethoxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylurea (115 mg) as an amorphous powder. 84.3 mg of amorphous powder was crystallized from AcOEt-IPE to give N′-[5-[4-(2-hydroxyethoxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-N,N-dimethylurea (79.5 mg) as a white powder.

Workup

  1. stirringthe mixture was stirred at 75° C. overnight
  2. temperatureto cool to ambient temperature
  3. customwas partitioned between ethyl acetate and H2O
  4. washThe combined organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative thin layer silica gel chromatography
  8. extractionThe separated silica gel was extracted with 10% MeOH/CHCl3
  9. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-fa8cb14694514a94bb398ee980c673ff
Source dataset
uspto-grants-2007_02
Patent number
US07183306B2

Reaction notes

Loading…