5-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamide → N-(2-{4-[3-isobutyryl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea

HRID 351278Notes

Reaction equation

HRID 351278 reaction equation
[CH:1]([Mg]Br)([CH3:3])[CH3:2].[NH2:6][C:7]([NH:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[N:21]=[C:20]([C:31](N(OC)C)=[O:32])[CH:19]=2)=[CH:14][CH:13]=1)=[O:8]>C1COCC1>[C:31]([C:20]1[CH:19]=[C:18]([C:15]2[CH:14]=[CH:13][C:12]([CH2:11][CH2:10][NH:9][C:7]([NH2:6])=[O:8])=[CH:17][CH:16]=2)[N:22]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[N:21]=1)(=[O:32])[CH:1]([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 865928625-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamideHCID 178418365HCID 178418365, compound2×

Product 1

HCID 21091090N-(2-{4-[3-isobutyryl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a 0.76M solution of isopropylmagnesium bromide in THF (2.0 ml) was added a solution of 5-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamide (130 mg) in THF (2 ml) dropwise at at 4° C. The mixture was stirred at ambient temperature overnight. Additional 0.76M solution of isopropylmagnesium bromide in THF (2.0 ml) was added and the mixture was stirred at 50° C. for 5 hours. The reaction mixture was cooled to ambient temperature and was quenched by adding saturated aqueous ammonium chloride solution. The mixture was extracted with AcOEt. The organic layer was washed with 1M HCl, saturated aqueous sodium bicarbonate solution, 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 MeOH/CHC3 10%. The separated silica gel was extracted with 10% MeOH/CHCl3 and the solvent was evaporated in vacuo to give N-(2-{4-[3-isobutyryl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea (30 mg) as amorphous powder.

Workup

  1. stirringthe mixture was stirred at 50° C. for 5 hours
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customwas quenched
  4. additionby adding saturated aqueous ammonium chloride solution
  5. extractionThe mixture was extracted with AcOEt
  6. washThe organic layer was washed with 1M HCl, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative thin layer silica gel chromatography
  10. extractionThe separated silica gel was extracted with 10% MeOH/CHCl3
  11. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-af88118d3803452a89550256c0872f81
Source dataset
uspto-grants-2007_02
Patent number
US07183306B2

Reaction notes

Loading…