1,2-Dichloro-3-isocyanatobenzene → 1-(5-tert-butyl-2-(5-oxo-1,4-diazepane-1-carbonyl)-1H-pyrrol-3-yl)-3-(2,3-dichloro-phenyl)urea

HRID 18928Notes

Reaction equation

HRID 18928 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[NH:5][C:6]=1[C:7]([N:9]1[CH2:15][CH2:14][C:13](=[O:16])[NH:12][CH2:11][CH2:10]1)=[O:8].[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[N:29]=[C:30]=[O:31]>C1COCC1.C(OCC)(=O)C>[C:17]([C:4]1[NH:5][C:6]([C:7]([N:9]2[CH2:15][CH2:14][C:13](=[O:16])[NH:12][CH2:11][CH2:10]2)=[O:8])=[C:2]([NH:1][C:30]([NH:29][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]([Cl:28])[C:22]=2[Cl:21])=[O:31])[CH:3]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 2

HCID 330501,2-Dichloro-3-isocyanatobenzeneHCID 586792281-(4-amino-2-tert-butyl-1H-pyrrole-5-carbonyl)-1,4-diazepan-5-one

Product 1

HCID 586791281-(5-tert-butyl-2-(5-oxo-1,4-diazepane-1-carbonyl)-1H-pyrrol-3-yl)-3-(2,3-dichloro-phenyl)ureaYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

The previously prepared 1-(4-amino-2-tert-butyl-1H-pyrrole-5-carbonyl)-1,4-diazepan-5-one (8 mg, 0.03 mmol) and 2,3 dichlorophenyl isocyanate (5 mg, 0.03 mmol) were dissolved in THF (2 mL) and heated at 70° C. for 2 hours. The reaction mixture was cooled down to room temperature, diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, dried and the solvent eliminated under vacuum. The crude product was purified by preparative thin layer chromatography using a mixture of dichloromethane:methanol 9:1 as elution solvent to afford 7.0 mg of 1-(5-tert-butyl-2-(5-oxo-1,4-diazepane-1-carbonyl)-1H-pyrrol-3-yl)-3-(2,3-dichloro-phenyl)urea as a white solid. 1H NMR (400 MHz, acetone-d6): δ (ppm) 9.60 (bs, 1H); 8.60 (d, 2H); 8.26 (d, 1H); 7.30 (t, 1H); 7.20 (d, 1H); 6.84 (t, 1H); 6.59 (d, 1H); 3.76 (m, 2H); 3.70 (m, 2H); 3.40 (m, 2H); 2.61 (m, 2H); 1.37 (s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. washwashed with saturated aqueous sodium bicarbonate
  3. customdried
  4. customThe crude product was purified by preparative thin layer chromatography
  5. additiona mixture of dichloromethane:methanol 9:1
  6. washas elution solvent

Sources & evidence

ORD record
ord-b6ec3c39b59d45f9a0e6cc05adbd1477
Source dataset
uspto-grants-2010_06
Patent number
US07741479B2

Reaction notes

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