Ethyl Acetate → N-{3-tert-Butyl-1-[4-(2-methoxyethoxy)phenyl]-1H-pyrazol-5-yl}-N'-[4-(pyridin-4-yloxy)-phenyl]urea

HRID 221889Notes

Reaction equation

HRID 221889 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH2:21])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[N:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)=[CH:24][CH:23]=1.C[CH2:37][O:38]C(C)=O>ClCCCl>[C:1]([C:5]1[CH:6]=[C:7]([NH:21][C:37]([NH:35][C:32]2[CH:33]=[CH:34][C:29]([O:28][C:25]3[CH:24]=[CH:23][N:22]=[CH:27][CH:26]=3)=[CH:30][CH:31]=2)=[O:38])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 115645894-(Pyridin-4-yloxy)anilineHCID 595579525-tert-butyl-2-[4-(2-methoxyethoxy)phenyl]2H-pyrazol-3-ylamine

Product 1

HCID 11706034N-{3-tert-Butyl-1-[4-(2-methoxyethoxy)phenyl]-1H-pyrazol-5-yl}-N'-[4-(pyridin-4-yloxy)-phenyl]ureaYield 35%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 5-tert-butyl-2-[4-(2-methoxyethoxy)phenyl]2H-pyrazol-3-ylamine (75 mg, 0.26 mmol) in anhydrous DCE (1.0 mL) was added CDT (37 mg, 0.31 mmol), and the reaction mixture was stirred at 60° C. for 6 h. A solution of 4-(pyridin-4-yloxy)phenylamine (48 mg, 0.26 mmol) in DCE (1.3 mL) was then added, and the mixture was stirred at 60° C. for 20 h. The reaction mixture was diluted into EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated at reduced pressure. The crude product was purified by HPLC and recrystallized from ether/DCM/hexane to give 45.2 mg (35%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 9.01 (s, 1H), 8.39 (d, J=4.8 Hz, 2H), 8.28 (s, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.7 Hz, 2H), 7.05 (d, J=8.7 Hz, 4H), 6.84 (d, J=4.8 Hz, 2H), 6.29 (s, 1H), 4.14 to 4.10 (m, 2H), 3.66 to 3.63 (m, 2H), 3.28 (s, 3H), 1.23 (s, 9H); MS LC-MS [M+H]+=502, RT=2.80 min.

Workup

  1. stirringthe mixture was stirred at 60° C. for 20 h
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at reduced pressure
  6. customThe crude product was purified by HPLC
  7. customrecrystallized from ether/DCM/hexane

Sources & evidence

ORD record
ord-40a93ef6269c45b5a8654d94d4dba62d
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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