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

HRID 2080961Notes

Reaction equation

HRID 2080961 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=O)[CH2:5][N:4]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=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.CN(C)C=O>[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[N:15]=[CH:14][CH:13]=[CH:12][N:11]=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-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrateHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 671033483-Methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylic acid

Product 1

HCID 25097731N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxamideYield 16.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A suspension of crude 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylic acid (0.6 mmol) in dichloromethane (10 ml) was treated with 1-hydroxybenzotriazole hydrate (98 mg, 0.72 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.72 mmol) and N-ethyl morpholine (0.3 ml, 2.4 mmol) was stirred at room temperature for 10 minutes. {[2-Chloro-3-(trifluoromethyl)phenyl]methyl}amine (126 mg, 0.6 mmol) was added. The reaction was diluted with dichloromethane (10 ml) and N,N-dimethylformamide (1 ml) and stirred at room temperature for 18 hours. Additional 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.72 mmol) was added and the suspension was stirred at room temperature for 5 days. The mixture was diluted with dichloromethane and the solution was washed with saturated sodium hydrogen carbonate solution, water, citric acid solution, water and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC. The solid was triturated with ether/hexanes, collected and dried to give N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxamide (42 mg), LC/MS [M+H]+=414, retention time=2.30 minutes.

Workup

  1. stirringstirred at room temperature for 18 hours
  2. stirringthe suspension was stirred at room temperature for 5 days
  3. washthe solution was washed with saturated sodium hydrogen carbonate solution, water, citric acid solution, water and brine
  4. customdried
  5. customevaporated
  6. customThe residue was purified
  7. customThe solid was triturated with ether/hexanes
  8. customcollected
  9. customdried

Sources & evidence

ORD record
ord-1138298667df49ff89c5183beac46eb6
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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