Ethylmorpholine → N-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxamide

HRID 2080969Notes

Reaction equation

HRID 2080969 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=O)[CH2:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[C:3]1=[O:16].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N1CCOCC1)C.[Cl:48][C:49]1[C:54]([C:55]([F:58])([F:57])[F:56])=[CH:53][CH:52]=[CH:51][C:50]=1[CH2:59][NH2:60]>ClCCl.CO>[Cl:48][C:49]1[C:54]([C:55]([F:57])([F:58])[F:56])=[CH:53][CH:52]=[CH:51][C:50]=1[CH2:59][NH:60][C:7]([CH:6]1[CH2:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[C:3](=[O:16])[N:2]1[CH3:1])=[O:9]

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 671036703-Methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxylic acid

Product 1

HCID 25097733N-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxamideYield 8.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of crude 3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxylic acid (0.8 mmol), 1-hydroxybenzotriazole hydrate (147 mg, 0.96 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (184 mg, 0.96 mmol), and N-ethyl morpholine (0.307 ml, 2.4 mmol) in dichloromethane (15 ml) was stirred at room temperature for 10 minutes. A solution of {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (168 mg, 0.8 mmol) in dichloromethane (1 ml) was added and the reaction stirred at room temperature for 4 hours. The mixture was partitioned between dichloromethane and saturated sodium hydrogen carbonate solution. The organic phase was separated, washed with water and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC. The solid was dissolved in methanol (5 ml) and anhydrous HCl in ether (1M, 0.5 ml) was added and the solution was evaporated. The resulting solid was collected, washed with ether and dried to give a pale yellow solid. The solid was dissolved in methanol and applied to a SCX ion exchange cartridge and washed with methanol and then 2M ammonia in methanol. The basic fractions were combined and evaporated and the resulting residue was triturated with ether, collected and dried to give N-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxamide (27 mg, 8%). LC/MS [M+H]+=413, retention time=1.96 minutes.

Workup

  1. stirringthe reaction stirred at room temperature for 4 hours
  2. customThe mixture was partitioned between dichloromethane and saturated sodium hydrogen carbonate solution
  3. customThe organic phase was separated
  4. washwashed with water and brine
  5. customdried
  6. customevaporated
  7. customThe residue was purified
  8. dissolutionThe solid was dissolved in methanol (5 ml)
  9. additionanhydrous HCl in ether (1M, 0.5 ml) was added
  10. customthe solution was evaporated
  11. customThe resulting solid was collected
  12. washwashed with ether
  13. customdried
  14. customto give a pale yellow solid
  15. washwashed with methanol
  16. customevaporated
  17. customthe resulting residue was triturated with ether
  18. customcollected
  19. customdried

Sources & evidence

ORD record
ord-6eb63ff24b89415096c1eaa86829654e
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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