Diisopropylethylamine → N-[(2-chloro-6-methylphenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester

HRID 895924Notes

Reaction equation

HRID 895924 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]([CH3:38])[C:30]=1[C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[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:34]([CH3:38])=[CH:35][CH:36]=[CH:37][C:29]=1[Cl:28])=[O:32]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 888702-Chloro-6-methylbenzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 697160064-[1,6-Dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-phenylalanine methyl ester hydrochloride

Product 1

HCID 69714689N-[(2-chloro-6-methylphenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl esterYield 75.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester hydrochloride salt (100 mg, 0.25 mmol), 2-chloro-6-methylbenzoic acid (60 mg, 0.35 mmol) and HBTU (132 mg, 0.35 mmol) in DMF (2 mL) was added DIEA (174 μL, 1.0 mmol) at room temperature. The resulting mixture was stirred for 72 h. Then, the mixture was poured into water (25 mL) and was extracted with ethyl acetate (2×15 mL). The combined ethyl acetate extracts were washed successively with 0.5 N HCl (25 mL), saturated NaHCO3 solution (25 mL), brine solution (25 mL) and were dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration gave the crude product which was purified by silica gel chromatography using a Biotage (40 s) column to afford 98 mg (75% yield) of N-[(2-chloro-6-methylphenyl)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 C26H24ClF3N2O4 (M+Na) 543.1268. found 543.1275. b) Preparation of N-[(2-chloro-6-methylphenyl)carbonyl]-4-[1,6-dimethyl-4-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine

Workup

  1. extractionwas extracted with ethyl acetate (2×15 mL)
  2. washThe combined ethyl acetate extracts were washed successively with 0.5 N HCl (25 mL), saturated NaHCO3 solution (25 mL), brine solution (25 mL)
  3. dry with materialwere dried over anhydrous magnesium sulfate
  4. filtrationFiltration of the drying agent and concentration
  5. customgave the crude product which
  6. customwas purified by silica gel chromatography
  7. customa Biotage (40 s) column

Sources & evidence

ORD record
ord-a9e07964df944d89ab8076bed512fe57
Source dataset
uspto-grants-2005_07
Patent number
US06916933B2

Reaction notes

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