Hydrochloric Acid → HCID 67103613, compound

HRID 2080993Notes

Reaction equation

HRID 2080993 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[CH2:10][NH:11][C:12]([CH:14]1[CH2:18][NH:17][C:16](=[O:19])[N:15]1[CH3:20])=[O:13].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.[H-].[Na+].Cl>CN(C=O)C.ClCCl.CO.ClCCl.CCOCC>[ClH:1].[Cl:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[CH2:10][NH:11][C:12]([CH:14]1[CH2:18][N:17]([CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[C:16](=[O:19])[N:15]1[CH3:20])=[O:13]

Participants

10

Reactant 5

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 25098282N-[(2-Chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

Product 1

HCID 67103613HCID 67103613, compoundYield 8%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (100 mg, 0.33 mmol) (prepared as described in Example 28) and potassium carbonate (91 mg, 0.66 mmol) in DMF (1 ml) was stirred at room temperature for 10 minutes and 4-(2-chloroethyl)morpholine hydrochloride (61 mg, 0.33 mmol) was added. The mixture was stirred for 30 minutes and then heated at 60° C. for 3 h and 80° C. for 2 h. The mixture was cooled to room temperature and sodium hydride (40 mg, 60% dispersion in oil, 1 mmol) was added and the mixture heated at 50° C. for 16 h. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The solution was washed with saturated sodium hydrogen carbonate solution and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC to give two components with same molecular ion. Each component was converted to the corresponding HCl salt by dissolving the product from mass-directed automated HPLC in methanol/dichloromethane, adding an excess of 1M HCl in ether, evaporating the solvent, co-evaporating the residue with methanol and ether. The residue was triturated with ether/heptane and the solid collected and dried to give N-[(2-Chloro-3,4-difluorophenyl)methyl]-3-methyl-1-[2-(4-morpholinyl)ethyl]-2-oxo-4-imidazolidinecarboxamide hydrochloride (22 mg, 15%) (LC/MS [M+H]+=417, retention time=1.40 minutes) and N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-[2-(4-morpholinyl)ethyl]-2-oxo-4-imidazolidinecarboxamide hydrochloride (6 mg, 4%) (LC/MS [M+H]+=417, retention time=1.55 minutes).

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. temperatureheated at 60° C. for 3 h and 80° C. for 2 h
  3. temperatureThe mixture was cooled to room temperature
  4. temperaturethe mixture heated at 50° C. for 16 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. washThe solution was washed with saturated sodium hydrogen carbonate solution and brine
  7. customdried
  8. customevaporated
  9. customThe residue was purified
  10. customto give two components with same molecular ion
  11. dissolutionby dissolving the product
  12. customevaporating the solvent
  13. customThe residue was triturated with ether/heptane
  14. customthe solid collected
  15. customdried

Sources & evidence

ORD record
ord-42db1fe805df4331aa694928dc0af9d8
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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