Ethyl Acetate → 4-(3-Tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}-pyrazol-1-yl)benzoic acid methyl ester

HRID 1174851Notes

Reaction equation

HRID 1174851 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([NH2:15])=[CH:13][C:12]([C:16]([CH3:19])([CH3:18])[CH3:17])=[N:11]2)=[CH:6][CH:5]=1.C1N=CN([C:26]([N:28]2C=N[CH:30]=[CH:29]2)=[O:27])C=1.[N:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]2[CH:45]=CC(N)=[CH:42][CH:41]=2)=[CH:35][CH:34]=1.CCOC(C)=O>ClCCCl>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:14]([NH:15][C:26]([NH:28][C:29]3[CH:30]=[CH:45][C:40]([O:39][C:36]4[CH:37]=[CH:38][N:33]=[CH:34][CH:35]=4)=[CH:41][CH:42]=3)=[O:27])=[CH:13][C:12]([C:16]([CH3:17])([CH3:19])[CH3:18])=[N:11]2)=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 2973426methyl 4-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)benzoateHCID 115645894-(Pyridin-4-yloxy)aniline

Product 1

HCID 536301834-(3-Tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}-pyrazol-1-yl)benzoic acid methyl esterYield 68.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a suspension of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)benzoic acid methyl ester (1.89 g, 6.93 mmol) in anhydrous DCE (10 mL) was added CDI (1.24 g, 7.62 mmol), and the mixture was stirred at room temperature for 16 h. A suspension of 4-(pyridin-4-yloxy)phenylamine (1.29 g, 6.93 mmol; Dumas et al., U.S. pat. appl. US2002065296 (2002)) in DCE was then added, and the mixture was stirred at room temperature for 4 h. The reaction was diluted into EtOAc. The organic layer was washed with water and brine, dried over MgSO4, filtered, and concentrated at reduced pressure. The crude product was purified by MPLC (15% EtOAc/hexane) to give 2.3 g (68%) of the title compound as a white solid. 1H-NMR (acetone-d6) δ 8.64 (s, 1H), 8.44 (d, J=9.0 Hz, 2H), 8.12 (d, J=9.0 Hz, 2H), 8.01 (s, 1H), 7.61 (d, J=9.0 Hz, 2H), 7.81 (d, J=9.0 Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 6.86 (d, J=6.0 Hz, 2H), 6.48 (s, 1H), 3.91 (s, 3H), 1.34 (s, 9H); MS LC-MS [M+H]+=486, RT=2.50 min.

Workup

  1. additionwas then added
  2. stirringthe mixture was stirred at room temperature for 4 h
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customThe crude product was purified by MPLC (15% EtOAc/hexane)

Sources & evidence

ORD record
ord-a67f3bc71dd944398934f7e30706c369
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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