1,1'-Carbonyldiimidazole → HCID 86010015, compound

HRID 1244308Notes

Reaction equation

HRID 1244308 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([OH:8])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[CH:25][C:24]=1[NH2:35]>CN(C=O)C>[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)=[CH:25][C:24]=1[NH:35][C:6]([C:2]1[NH:1][CH:5]=[CH:4][N:3]=1)=[O:8]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 5743211H-Imidazole-2-carboxylic acidHCID 113677782-Methoxy-5-morpholinoaniline

Product 1

HCID 86010015HCID 86010015, compoundYield 9.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 1.0 g of imidazole-2-carboxylic acid (8.9 mmol) in 15 ml DMF was added 1.6 g of CDI (9.8 mmol) and stirred at ambient temperature for 1 h. Then the mixture was refluxed for 30 min. After cooling to ambient temperature, 2.0 g of 2-methoxy-5-morpholin-4-yl-phenylamine (9.8 mmol) were added and the reaction mixture was heated to reflux for 16 h. The mixture was evaporated and the residue taken up in water (40 ml) and extracted 3 times with ethyl acetate. The combined organic phases were dried on sodium carbonate, evaporated and the residue subjected to column chromatography (silica gel, ethyl acetate/hexanes 2:1). 0.25 g 1H-imidazole-2-carboxylic acid (2-methoxy-5-morpholin-4-yl-phenyl)-amide (9%) were obtained as a white solid; M.p.: 227–230° C. 0.2 g of 1H-Imidazole-2-carboxylic acid (2-methoxy-5-morpholin-4-yl-phenyl)-amide (0.66 mmol) were taken up in toluene (8.0 ml) and treated with 0.8 g of Lawesson reagent (2.0 mmol). The reaction mixture was heated to reflux for 22 h. After cooling to ambient temperature, water (25 ml) was added and the mixture was extracted 3 times with ethyl acetate. The combined organic phases were dried on sodium carbonate, evaporated and the residue subjected to column chromatography (silica gel, ethyl acetate/hexanes 1:1). 0.125 g of 1H-imidazole-2-carbothioic acid (2-methoxy-5-morpholin-4-yl-phenyl)-amide (59%) was obtained as a yellow foam; MS (ISP): m/e=319 (M+H+).

Workup

  1. temperatureThen the mixture was refluxed for 30 min
  2. temperatureAfter cooling to ambient temperature
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for 16 h
  5. customThe mixture was evaporated
  6. extractionextracted 3 times with ethyl acetate
  7. customThe combined organic phases were dried on sodium carbonate
  8. customevaporated

Sources & evidence

ORD record
ord-8fdb618f5be04186845c9617308e653d
Source dataset
uspto-grants-2006_10
Patent number
US07122545B2

Reaction notes

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