Pyridine → N-(2-Methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(4-pyridinylthio)phenyl)urea

HRID 2110084Notes

Reaction equation

HRID 2110084 reaction equation
N1C=CC=CC=1.[C:7](Cl)(Cl)=[O:8].[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:14]=1[NH2:15].[N:24]1[CH:29]=[CH:28][C:27]([S:30][C:31]2[CH:32]=[C:33]([CH:35]=[CH:36][CH:37]=2)[NH2:34])=[CH:26][CH:25]=1>C(Cl)Cl.O.C1(C)C=CC=CC=1>[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:16][C:14]=1[NH:15][C:7]([NH:34][C:33]1[CH:35]=[CH:36][CH:37]=[C:31]([S:30][C:27]2[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=2)[CH:32]=1)=[O:8]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 6006372-Methoxy-5-(trifluoromethyl)anilineHCID 230230853-(4-Pyridinylthio)aniline

Product 1

HCID 10025068N-(2-Methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(4-pyridinylthio)phenyl)urea

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of pyridine (0.61 mL, 7.5 mmol, 3.0 equiv) and phosgene (20% in toluene; 2.65 mL, 5.0 mmol, 2.0 equiv) in CH2Cl2 (20 mL) was added 2-methoxy-5-(trifluoromethyl)aniline (0.48 g, 2.5 mmol) at 0° C. The resulting mixture was allowed warm to room temp. stirred for 3 h, then treated with anh. toluene (100 mL) and concentrated under reduced pressure. The residue was suspended in a mixture of CH2Cl2 (10 mL) and anh. pyridine (10 mL) and treated with 3-(4-pyridinylthio)aniline (0.61 g, 2.5 mmol, 1.0 equiv). The mixture was stirred overnight at room temp., then poured into water (50 mL) and extracted with CH2Cl2 (3×25 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was dissolved in a minimal amount of CH2Cl2 and treated with pet. ether to give the desired product as a white precipitate (0.74 g, 70%): mp 202° C.; TLC (5% acetone/95% CH2Cl2) Rf 0.09; 1H-NMR (DMSO-d6) δ 7.06 (d, J=5.5 Hz, 2H), 7.18 (dd, J=2.4, 4.6 Hz, 2H), 7.31 (dd, J=2.2, 9.2 Hz, 1H), 7.44 (d, J=5.7 Hz, 1H), 7.45 (s, 1H), 7.79 (d, J=2.2 Hz, 1H), 8.37 (s, 2H), 8.50 (dd, J=2.2, 9.2 Hz, 2H), 9.63 (s, 1H), 9.84 (s, 1H); FAB-MS m/z 420 ((M+H)+, 70%). B2b. General Method for Reaction of an Aryl Amine with Phosgene Followed by Addition of a Second Aryl Amine

Workup

  1. temperatureThe resulting mixture was allowed warm to room temp.
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was suspended in a mixture of CH2Cl2 (10 mL) and anh. pyridine (10 mL)
  4. stirringThe mixture was stirred overnight at room temp.
  5. extractionextracted with CH2Cl2 (3×25 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in a minimal amount of CH2Cl2
  9. additiontreated with pet. ether

Sources & evidence

ORD record
ord-bff74986182d4dd9862d364fcf33afca
Source dataset
uspto-grants-2009_04
Patent number
US07517880B2

Reaction notes

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