Ammonia → N-[(2,4-dichlorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamide

HRID 2081056노트

반응식

HRID 2081056 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([CH:13]1[CH2:17][NH:16][C:15](=[O:18])[N:14]1[CH3:19])=[O:12].I[C:21]1[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)[C@@H]1CCCC[C@H]1N.N>O1CCOCC1.[Cu]I.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([CH:13]1[CH2:17][N:16]([C:21]2[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=2)[C:15](=[O:18])[N:14]1[CH3:19])=[O:12]

참가 물질

10

반응물 5

HCID 222AmmoniaHCID 62657Potassium Phosphate, TribasicHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 133340655-Iodo-1-methyl-1H-pyrazoleHCID 25098283N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

생성물 1

HCID 25095958N-[(2,4-dichlorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamide수율 16%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

To a stirred mixture of N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (200 mg, 0.662 mmol) (prepared as described in Example 30), 5-iodo-1-methyl-1H-pyrazole (165 mg, 0.794 mmol) in 1,4-dioxane (20 ml) was added potassium phosphate (703 mg, 3.31 mmol), copper (I) iodide (126 mg, 0.662 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.104 ml, 0.662 mmol) and the reaction mixture was heated at reflux under argon for 18 hours. After cooling to room temperature, ethyl acetate (20 ml), water (10 ml) and 0.880 ammonia solution (5 ml) were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×20 ml). The organic extracts were combined, washed with citric acid solution (20 ml), water (10 ml) and brine (10 ml), dried and evaporated. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane followed by mass-directed automated HPLC to give N-[(2,4-dichlorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamide (40 mg, 16%). LC/MS [M+H]+=382, retention time=2.12 minutes.

후처리

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux under argon for 18 hours
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×20 ml)
  5. washwashed with citric acid solution (20 ml), water (10 ml) and brine (10 ml)
  6. customdried
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 0-10% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-d056dc8691224aacb77204cd0b2916db
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07932282B2

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