3-Bromo-1-methyl-1,2-dihydropyridin-2-one → N-[(1,1-dimethylethoxyl)carbonyl]-4-(1-methyl-2-oxo-3-pyridinyl)-L-phenylalanine methyl ester

HRID 895900Notes

Reaction equation

HRID 895900 reaction equation
Br[C:2]1[C:3](=[O:9])[N:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.[CH3:10][O:11][C:12](=[O:42])[C@H:13]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Sn](CCCC)(CCCC)CCCC)=[CH:25][CH:24]=1)[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>CN(C=O)C.ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:10][O:11][C:12](=[O:42])[C@H:13]([CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:2]2[C:3](=[O:9])[N:4]([CH3:8])[CH:5]=[CH:6][CH:7]=2)=[CH:27][CH:28]=1)[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16]

Participants

6

Reactant 2

HCID 130240253-Bromo-1-methyl-1,2-dihydropyridin-2-oneHCID 59912887N-Boc-4-(Tributylstannyl)-L-phenylalanine Methyl Ester

Product 1

HCID 69715223N-[(1,1-dimethylethoxyl)carbonyl]-4-(1-methyl-2-oxo-3-pyridinyl)-L-phenylalanine methyl esterYield 33.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 3-bromo-1-methyl-2-pyridone (94 mg, 0.50 mmol) and N-[(1,1-dimethylethoxy)carbonyl]-4-[(tributyl)stannyl]-L-phenylalanine methyl ester (284 mg, 0.50 mmol) in DMF (3 mL) was deoxygenated by alternately freezing the mixture in a liquid nitrogen bath under vacuum and thawing under argon (3×). bis(triphenylphosphine)palladium dichloride (40 mg, 0.057 mmol) was added and the mixture was heated to 90° C. for 3 hr as the mixture turned dark. TLC indicated that the reaction was not complete and an additional 20 mg portion of the catalyst was added and heating continued for 4 hr. The mixture was allowed to cool and was diluted with dichloromethane (20 mL) and was filtered through a pad of celite. The filtrate was evaporated to dryness and the residue was dissolved in 1:1 ether:ethyl acetate (20 mL). The solution was washed with water (1×10 mL), 5% potassium fluoride (2×5 mL) and water (1×10 mL) and was dried (MgSO4). The residue obtained upon concentration was chromatographed over 25 g of silica gel eluting with 4:6 ethyl acetate:hexane to give N-[(1,1-dimethylethoxyl)carbonyl]-4-(1-methyl-2-oxo-3-pyridinyl)-L-phenylalanine methyl ester (64 mg, 33%). LRMS-Electrospray: m/z positive ion, 795 (2M+Na) 409 (M+Na) 387 (M+H). HRMS: Obs. Mass 387.1935. Calcd. Mass 387.1920 (M+H).

Workup

  1. additionan additional 20 mg portion of the catalyst was added
  2. temperatureheating
  3. temperatureto cool
  4. filtrationwas filtered through a pad of celite
  5. customThe filtrate was evaporated to dryness
  6. dissolutionthe residue was dissolved in 1:1 ether
  7. washThe solution was washed with water (1×10 mL), 5% potassium fluoride (2×5 mL) and water (1×10 mL)
  8. dry with materialwas dried (MgSO4)
  9. customThe residue obtained upon concentration
  10. customwas chromatographed over 25 g of silica gel eluting with 4:6 ethyl acetate

Sources & evidence

ORD record
ord-40081511f63542c891b1e19d8ac4a920
Source dataset
uspto-grants-2005_07
Patent number
US06916933B2

Reaction notes

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