Dichloromethane → N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamide

HRID 2081010Notes

Reaction equation

HRID 2081010 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.[CH3:8][N:9]1[CH:13]([C:14]([OH:16])=O)[CH2:12][N:11]([C:17]2[N:18]=[CH:19][N:20]([CH3:22])[CH:21]=2)[C:10]1=[O:23].Cl.C(N=C=N[CH2:30][CH2:31][CH2:32][N:33](C)C)C.C(N1[CH2:43][CH2:42]OCC1)C.[Cl:44][CH2:45]Cl>>[Cl:44][C:45]1[C:3]([C:2]([F:7])([F:6])[F:1])=[CH:43][CH:42]=[CH:30][C:31]=1[CH2:32][NH:33][C:14]([CH:13]1[CH2:12][N:11]([C:17]2[N:18]=[CH:19][N:20]([CH3:22])[CH:21]=2)[C:10](=[O:23])[N:9]1[CH3:8])=[O:16]

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 7525EthylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671037233-Methyl-1-(1-methyl-1h-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxylic acid trifluoroacetate salt

Product 1

HCID 25094620N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamideYield 10.6%

Procedure

A solution of 3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxylic acid trifluoroacetate salt (145 mg, 0.647 mmol) in dichloromethane (4 ml) was treated with 1-hydroxyorthobenzatriazole hydrate (119 mg, 0.776 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (149 mg, 0.776 mmol) & N-ethylmorpholine (0.491 ml, 3.88 mmol) and the mixture stirred at room temp for 10 minutes. 1-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}amine (136 mg, 0.647 mmol) was then added and the reaction stirred at room temp over the weekend. The reaction was diluted with dichloromethane and washed with 3N citric acid, saturated sodium hydrogen carbonate solution, water and brine, separated through a hydrophobic frit and the organic layer reduced under vacuum. The residue was purified by mass-directed automated HPLC and freeze dried to give N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamide (30 mg, 10.6% yield). LC/MS [M+H]+=416, retention time=1.92 minutes.

Workup

  1. stirringthe reaction stirred at room temp over the weekend
  2. washwashed with 3N citric acid, saturated sodium hydrogen carbonate solution, water and brine
  3. customseparated through a hydrophobic frit
  4. customThe residue was purified
  5. customfreeze dried

Sources & evidence

ORD record
ord-fcda682adf0e4c45809e9ca55536fcce
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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