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

HRID 1247446Notes

Reaction equation

HRID 1247446 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.CN1CCOCC1.[CH3:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=[O:34])[CH:29]=[CH:30][CH:31]=1>C1COCC1>[CH3:25][C:26]1[CH:27]=[C:28]([NH:32][C:33]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:9]=3[CH2:10][NH:11][C:12]4=[O:17])=[CH:6][CH:7]=2)=[O:34])[CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 69303m-Tolyl isocyanateHCID 219075114-(4-Aminophenyl)isoindolin-1-one

Product 1

HCID 53298801-(3-methylphenyl)-3-[4-(1-oxo-2,3-dihydro-1H-isoindol-4-yl)phenyl]ureaYield 94.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

An 0° C. suspension of Example 1D (1.94 g, 8.68 mmol) in THF (44 mL) was sequentially treated dropwise with N-methylmorpholine (0.95 mL, 8.68 mmol) and 3-methylphenyl isocyanate (1.12 mL, 8.68 mmol). The mixture was stirred for 1 hour, diluted with THF (20 mL), stirred at room temperature for 3 hours, and quenched with water (20 mL). The organic phase was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was suspended in 5% methanol/dichloromethane and filtered. The filter cake was washed with dichloromethane and dried to provide 2.94 g of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.29 (s, 3H), 4.52 (s, 2H), 6.80 (d, J=7.5 Hz, 1H), 7.17 (t, J=7.6 Hz, 1H), 7.23–7.27 (m, 1H), 7.31 (s, 1H), 7.53–7.60 (m, 5H), 7.64–7.67 (m, 2H), 8.63 (s, 1H), 8.65 (s, 1H), 8.80 (s, 1H); MS (ESI(+)) m/e 358.1 (M+H)+.

Workup

  1. stirringstirred at room temperature for 3 hours
  2. customquenched with water (20 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. filtrationfiltered
  8. washThe filter cake was washed with dichloromethane
  9. customdried

Sources & evidence

ORD record
ord-85bd666d1a554a95ba8202dc4ad670a4
Source dataset
uspto-grants-2006_10
Patent number
US07129260B2

Reaction notes

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