Ethyl 3-{3-t-butyl-5-[3-(4-chlorophenyl)ureido]-1h-pyrazol-1-yl}benzoate → 1-{5-t-Butyl-2-[3-(1-hydroxy-1-methyl-ethyl)-phenyl]-2h-pyrazol-3-yl}-3-(4-chloro-phenyl)-urea

HRID 492018

Reaction equation

HRID 492018 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[O:12])[N:7]([C:21]2[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=2)C(OCC)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C[Mg]Br.[C:35]1([CH3:41])C=CC=C[CH:36]=1.C1C[O:45]CC1>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)=[O:12])[N:7]([C:21]2[CH:31]=[CH:30][CH:29]=[C:23]([C:35]([OH:45])([CH3:41])[CH3:36])[CH:22]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 21867337Ethyl 3-{3-t-butyl-5-[3-(4-chlorophenyl)ureido]-1h-pyrazol-1-yl}benzoateHCID 22635083Tetrahydrofuran tolueneHCID 178418573HCID 178418573, compound

Product 1

HCID 184498651-{5-t-Butyl-2-[3-(1-hydroxy-1-methyl-ethyl)-phenyl]-2h-pyrazol-3-yl}-3-(4-chloro-phenyl)-ureaYield 81.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example C (220 mg, 0.5 mmol) in dry THF (20 mL) was added dropwise a solution of methyl magnesium bromide in toluene/THF (3.6 mL, 5.0 mmol) at −78° C. under N2. After stirring for 1 h, the mixture was allowed to rise to RT and stirred for another 2 h. The reaction mixture was quenched with saturated NH4Cl and aqueous HCl solution (10%), and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), the solvent was removed in vacuo and the residue was purified by column chromatography to afford 1-{5-t-butyl-2-[3-(1-hydroxy-1-methyl-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-(4-chloro-phenyl)-urea (174 mg, 81%). 1H NMR (DMSO-d6): 9.11 (s, 1H), 8.34 (s, 1H), 7.59 (s, 1H), 7.46 (t, J=8.8 Hz, 1H), 7.43-7.40 (m, 3H), 7.31-7.28 (m, 3H), 6.34 (s, 1H), 5.13 (s, 1H), 1.42 (s, 6H), 1.27 (s, 9H); MS (ESI) m/z: 428 (M+H+).

Workup

  1. customto rise to RT
  2. stirringstirred for another 2 h
  3. customThe reaction mixture was quenched with saturated NH4Cl and aqueous HCl solution (10%)
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was removed in vacuo
  8. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-20086eb753f74874b7ebd7a7c3b4351f
Source dataset
uspto-grants-2009_05
Patent number
US07531566B2

Linked notes

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