Bromocyclopropane → N-(2-{4-[3-(cyclopropylcarbonyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea

HRID 351279Notes

Reaction equation

HRID 351279 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.C1(Br)CC1.[Mg].[NH2:11][C:12]([NH:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:27]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[N:26]=[C:25]([C:36](N(OC)C)=[O:37])[CH:24]=2)=[CH:19][CH:18]=1)=[O:13]>C1COCC1>[CH:1]1([C:36]([C:25]2[CH:24]=[C:23]([C:20]3[CH:21]=[CH:22][C:17]([CH2:16][CH2:15][NH:14][C:12]([NH2:11])=[O:13])=[CH:18][CH:19]=3)[N:27]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[N:26]=2)=[O:37])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 78037BromocyclopropaneHCID 5462224MagnesiumHCID 865928625-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamideHCID 178418630HCID 178418630, compound

Product 1

HCID 21091074N-(2-{4-[3-(cyclopropylcarbonyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of cyclopropylmagnesium bromide, which was prepared from cyclopropyl bromide (257 ml) and magnesium (57 mg) in THF (1 ml) as usual method, was added a solution of 5-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamide (90 mg) in THF (3 ml) dropwise at ambient temperature. 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-(cyclopropylcarbonyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea (23 mg) as a powder.

Workup

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

Sources & evidence

ORD record
ord-34b4645bd74949f7813239f16899fdd3
Source dataset
uspto-grants-2007_02
Patent number
US07183306B2

Reaction notes

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