Dimethylformamide → (R)-3-(5-Bromo-thiophen-2-yl)-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

HRID 1625466Notes

Reaction equation

HRID 1625466 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH2:4][C@@H:5]([NH:11][C:12]([C:14]1[C:15](=[O:29])[N:16]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([F:28])[CH:22]=2)[CH:17]=[CH:18][CH:19]=1)=[O:13])[C:6]1[S:7][CH:8]=[CH:9][CH:10]=1.CN(C)C=O.[Br:36]N1C(=O)CCC1=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C@H:5]([C:6]1[S:7][C:8]([Br:36])=[CH:9][CH:10]=1)[NH:11][C:12]([C:14]1[C:15](=[O:29])[N:16]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([F:28])[CH:22]=2)[CH:17]=[CH:18][CH:19]=1)=[O:13]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 67184N-bromobutanimideHCID 68606760(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-thiophen-2-yl-propionic acid methyl ester

Product 1

HCID 68606715(R)-3-(5-Bromo-thiophen-2-yl)-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-thiophen-2-yl-propionic acid methyl ester (0.420 g, 0.000971 mol;) was dissolved in N,N-Dimethylformamide (20 mL, 0.2 mol;) and N-Bromosuccinimide (0.19 g, 0.0011 mol;) was added. The reaction was allowed to stir o/n and LC-MS showed formation of product at 1.87 510.95. The reaction was diluted with methylene chloride and washed 1× with saturated bicarbonate, 1× with 5% citric acid, and 1× with brine. The organic layer was then dried with magnesium sulfate and concentrated to give the crude material. The crude was dissolved in methylene chloride and purified by combiflash 0-100% hexanes/ethyl acetate to give the pure product. ES (+) MS m/e=510.95

Workup

  1. washwashed 1× with saturated bicarbonate, 1× with 5% citric acid, and 1× with brine
  2. dry with materialThe organic layer was then dried with magnesium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-50d20f586c42495ea9c798b7f20349bb
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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