2,6-Dichlorobenzoyl chloride → N-[(2,6-dichlorophenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester

HRID 1936482Notes

Reaction equation

HRID 1936482 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:27])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:26])[N:16]([CH3:25])[C:17]([CH3:24])=[CH:18][C:19]=2[C:20]([F:23])([F:22])[F:21])=[CH:10][CH:9]=1)[NH2:6].[Cl:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:30]=1[C:31](Cl)=[O:32].CCN(C(C)C)C(C)C>ClCCl>[CH3:2][O:3][C:4](=[O:27])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[C:15](=[O:26])[N:16]([CH3:25])[C:17]([CH3:24])=[CH:18][C:19]=2[C:20]([F:21])([F:22])[F:23])=[CH:12][CH:13]=1)[NH:6][C:31]([C:30]1[C:29]([Cl:28])=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:38])=[O:32]

Participants

5

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 697160064-[1,6-Dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-phenylalanine methyl ester hydrochloride

Product 1

HCID 69714407N-[(2,6-dichlorophenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester hydrochloride salt (150 mg, 0.37 mmol) and 2,6-dichlorobenzoyl chloride (85 mg, 0.4 mmol) in dichloromethane (6 mL) was added DIEA (257 μL, 1.48 mmol) at room temperature. After 5 min, a clear solution was obtained which was stirred for 48 h. Then, the mixture was concentrated and the residue was dissolved in ethyl acetate (50 mL). The ethyl acetate solution was washed with 0.5 N HCl (50 mL), saturated NaHCO3 solution (50 mL) and brine solution (50 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration gave crude product, which was purified by silica gel chromatography on a Biotage (40 m) column to give 190 mg (95% yield) of N-[(2,6-dichlorophenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester as an amorphous white solid. ES-HRMS m/e calcd for C25H21Cl2F3N2O4 (M+Na) 563.0724, found 563.0726.

Workup

  1. customa clear solution was obtained which
  2. concentrationThen, the mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  4. washThe ethyl acetate solution was washed with 0.5 N HCl (50 mL), saturated NaHCO3 solution (50 mL) and brine solution (50 mL)
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationFiltration of the drying agent and concentration
  7. customgave crude product, which
  8. customwas purified by silica gel chromatography on a Biotage (40 m) column

Sources & evidence

ORD record
ord-74e9eb72097c4b81b303ce77fc3d0641
Source dataset
uspto-grants-2002_05
Patent number
US06388084B1

Reaction notes

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