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

HRID 78333

Reaction equation

HRID 78333 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 stifling 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) δ 1.37 (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-74a8f08ce2e140a7b28ba7176f39a77d
Source dataset
uspto-grants-2014_09
Patent number
US08841330B2

Linked notes

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