1,1'-Carbonyldiimidazole → N-(5-(tert-butyl)-2-(2,5-dimethylpyrrolyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea

HRID 2078575Notes

Reaction equation

HRID 2078575 reaction equation
[CH:1]1N=C[N:3]([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])[CH:2]=1.[C:13]([C:17]1[CH:18]=[CH:19][C:20]([C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][C:25]=2[CH3:30])=C(C=1)N)([CH3:16])([CH3:15])[CH3:14].[CH3:31][NH:32][C:33]([C:35]1[CH:40]=[C:39]([O:41][C:42]2[CH:48]=CC(N)=[CH:44][CH:43]=2)[CH:38]=[CH:37][N:36]=1)=[O:34]>C(Cl)Cl.CCOC(C)=O>[C:13]([C:17]1[CH:18]=[CH:19][C:20]([C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][C:25]=2[CH3:30])=[C:9]([NH:8][C:6]([NH:3][C:2]2[CH:1]=[CH:48][C:42]([O:41][C:39]3[CH:38]=[CH:37][N:36]=[C:35]([C:33](=[O:34])[NH:32][CH3:31])[CH:40]=3)=[CH:43][CH:44]=2)=[O:7])[CH:10]=1)([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 166551294-(4-Aminophenoxy)-N-methylpicolinamideHCID 540501305-Tert-butyl-2-(2,5-dimethylpyrrolyl)aniline

Product 1

HCID 54135293N-(5-(tert-butyl)-2-(2,5-dimethylpyrrolyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)ureaYield 24.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
36 °C

Procedure

To a stirring solution of CDI (0.21 g, 1.30 mmol) in CH2Cl2 (2 mL) was added 5-(tert-butyl)-2-(2,5-dimethylpyrrolyl)aniline (Method A4, Step 2; 0.30 g, 1.24 mmol) in one portion. The resulting mixture was stirred at room temp. for 4 h, then 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline (0.065 g, 0.267 mmol) was then added in one portion. The resulting mixture was heated at 36° C. overnight, then cooled to room temp. and diluted with EtOAc (5 mL). The resulting mixture was sequentially washed with water (15 mL) and a 1N HCl solution (15 mL), dried (MgSO4), and filtered through a pad of silica gel (50 g) to afford N-(5-(tert-butyl)-2-(2,5-dimethylpyrrolyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea as a yellowish solid (0.033 g, 24%): TLC (40% EtOAc/60% hexane) Rf 0.24; 1H NMR (acetone-d6) δ1.37 (s, 9H), 1.89 (s, 6H), 2.89 (d, J=4.8 Hz, 3H), 5.83 (s, 2H), 6.87-7.20 (m, 6H), 7.17 (dd, 1H), 7.51-7.58 (m, 3H), 8.43 (d, J=5.4 Hz, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.80 (br s, 1H); HPLC ES-MS 512 ((M+H)+, 100%).

Workup

  1. temperaturecooled to room temp.
  2. washThe resulting mixture was sequentially washed with water (15 mL)
  3. dry with materiala 1N HCl solution (15 mL), dried (MgSO4)
  4. filtrationfiltered through a pad of silica gel (50 g)

Sources & evidence

ORD record
ord-8e4d2124f94d47ccb1c5d5580a23bace
Source dataset
uspto-grants-2011_04
Patent number
US07928239B2

Reaction notes

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