Methanol → 2-methoxy-5-(trifluoromethyl)phenyl-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl)urea

HRID 78332Notes

Reaction equation

HRID 78332 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[N:13]=[C:14]=[O:15].[NH2:16][C:17]1[CH:34]=[CH:33][C:20]([O:21][C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[C:27](=[O:31])[NH:26][C:25]3=[O:32])=[CH:19][CH:18]=1.CO>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[NH:13][C:14]([NH:16][C:17]1[CH:18]=[CH:19][C:20]([O:21][C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[C:27](=[O:31])[NH:26][C:25]3=[O:32])=[CH:33][CH:34]=1)=[O:15]

Participants

5

Reactant 3

HCID 887MethanolHCID 8826275-(4-Aminophenoxy)isoindoline-1,3-dioneHCID 11983909Benzene, 2-isocyanato-1-methoxy-4-(trifluoromethyl)-

Product 1

HCID 102387342-methoxy-5-(trifluoromethyl)phenyl-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl)ureaYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stifling solution of 2-methoxy-5-(trifluoromethyl)phenyl isocyanate (0.10 g, 0.47 mmol) in CH2Cl2 (1.5 mL) was added 5-(4-aminophenoxy)isoindoline-1,3-dione (Method A3, Step 3; 0.12 g, 0.47 mmol) in one portion. The resulting mixture was stirred for 12 h, then was treated with CH2Cl2 (10 mL) and MeOH (5 mL). The resulting mixture was sequentially washed with a 1N HCl solution (15 mL) and a saturated NaCl solution (15 mL), dried (MgSO4) and concentrated under reduced pressure to afford N-(2-methoxy-5-(trifluoromethyl)phenyl-N′-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl)urea as a white solid (0.2 g, 96%): TLC (70% EtOAc/30% hexane) Rf 0.50; 1H NMR (DMSO-d6) δ 3.95 (s, 3H), 7.31-7.10 (m, 6H), 7.57 (d, J=9.3 Hz, 2H), 7.80 (d, J=8.7 Hz, 1H), 8.53 (br s, 2H), 9.57 (s, 1H), 11.27 (br s, 1H); HPLC ES-MS 472.0 ((M+H)+, 100%).

Workup

  1. washThe resulting mixture was sequentially washed with a 1N HCl solution (15 mL)
  2. dry with materiala saturated NaCl solution (15 mL), dried (MgSO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ee5fbbf6db754a10af93fd525b127182
Source dataset
uspto-grants-2014_09
Patent number
US08841330B2

Reaction notes

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