Triethylamine → 1-methyl-1-(3-methylphenyl)-3-[4-(1-oxo-2,3-dihydro-1H-isoindol-4-yl)phenyl]urea

HRID 1247461Notes

Reaction equation

HRID 1247461 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][NH:11][C:12]3=[O:17])=[CH:4][CH:3]=1.C([N:20]([CH2:23]C)[CH2:21][CH3:22])C.ClC(Cl)(O[C:29](=[O:35])OC(Cl)(Cl)Cl)Cl>O1CCOCC1>[CH3:23][N:20]([C:21]1[CH:22]=[CH:3][CH:4]=[C:5]([CH3:8])[CH:6]=1)[C:29]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][NH:11][C:12]3=[O:17])=[CH:6][CH:7]=1)=[O:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 219075114-(4-Aminophenyl)isoindolin-1-one

Product 1

HCID 53298821-methyl-1-(3-methylphenyl)-3-[4-(1-oxo-2,3-dihydro-1H-isoindol-4-yl)phenyl]ureaYield 55.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of Example 1D (0.25 g, 1.1 mmol) in dioxane (3 mL) was sequentially treated with triethylamine (0.17 mL, 1.2 mmol) and triphosgene (0.11 g, 0.37 mmol), heated to 70° C. for 2 hours, and concentrated. The concentrate was resuspended in THF (3 mL), treated with N-methyltoluidine, stirred at room temperature for 18 hours, and partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography with 2% methanol/dichloromethane to give 76 mg (20% yield) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.34 (s, 3H); 3.27 (s, 3H); 4.50 (s, 2H); 7.08 (d, J=7.46 Hz, 1H); 7.12 (d, J=8.48 Hz, 1H); 7.17 (s, 1H); 7.31 (t, J=7.80 Hz, 1H); 7.48 (d, J=8.82 Hz, 2H); 7.57 (d, J=8.82 Hz, 3H); 7.62 (d, J=3.39 Hz, 1H); 7.65 (d, J=5.76 Hz, 1H); 8.24 (s, 1H); 8.64 (s, 1H). MS (ESI(+)) m/e 372 (M+H)+.

Workup

  1. concentrationconcentrated
  2. additiontreated with N-methyltoluidine
  3. custompartitioned between water and ethyl acetate
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washthe combined extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-3c63b6ee80d74d3bafa3834841287b6c
Source dataset
uspto-grants-2006_10
Patent number
US07129260B2

Reaction notes

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