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

HRID 2081038Notes

Reaction equation

HRID 2081038 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=O)[CH2:5][N:4]([C:10]2[CH:15]=[N:14][CH:13]=[CH:12][N:11]=2)[C:3]1=[O:16].C(N1CCOCC1)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)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>[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:15]=[N:14][CH:13]=[CH:12][N:11]=2)[C:3](=[O:16])[N:2]1[CH3:1])=[O:9]

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 671034553-Methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxylic acid

Product 1

HCID 25095176N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxamideYield 19.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxylic acid (145 mg, 0.561 mmol) and N-ethylmorpholine (0.426 ml, 3.36 mmol) in dichloromethane (5 ml) was added 1-hydroxybenzotriazole hydrate (86 mg, 0.561 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (107 mg, 0.561 mmol) and the reaction mixture was stirred for 10 minutes at room temperature. 1-[2-Chloro-3-(trifluoromethyl)phenyl]methanamine (141 mg, 0.673 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed with saturated sodium hydrogen carbonate solution, water and brine and separated by hydrophobic frit and the organic layer reduced under vacuum. The residue was purified by SP4 automated silica gel chromatography eluting with 10-100% ethyl acetate in isohexane to give N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxamide (45 mg, 19% yield). LC/MS [M+H]+=413, retention time=2.21 minutes.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. washwashed with saturated sodium hydrogen carbonate solution, water and brine
  3. customseparated by hydrophobic frit
  4. customThe residue was purified by SP4 automated silica gel chromatography
  5. washeluting with 10-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b4cfdb304ab04b56a09bcb4f275e9e3e
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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