Triethylamine → 4-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide

HRID 422757Notes

Reaction equation

HRID 422757 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:17]([OH:19])=O)=[CH:11][N:12]([CH3:16])[C:13](=[O:15])[CH:14]=2)=[C:4]([F:20])[CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:42]([O:44][CH2:45][CH2:46][O:47][NH2:48])=[CH2:43].CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[CH:42]([O:44][CH2:45][CH2:46][O:47][NH:48][C:17]([C:10]1[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[F:20])=[CH:14][C:13](=[O:15])[N:12]([CH3:16])[CH:11]=1)=[O:19])=[CH2:43]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 115809254-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acidHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamine

Product 1

HCID 115463694-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amideYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.120 g, 0.352 mmol), EDCI (0.10 g, 0.53 mmol), and HOBt (0.071 g, 0.53 mmol) in DMF (5 mL) was stirred for 3 hours. O-(2-Vinyloxy-ethyl)-hydroxylamine (0.071 mL, 0.70 mmol) was added followed by Et3N (0.098 mL, 0.70 mmol). After 2 hours, the reaction mixture was diluted with EtOAc and washed with saturated NH4Cl solution, saturated NaHCO3 solution and brine. The organic layer was dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography (3% MeOH in methylene chloride) gave 0.078 g (52%) clean desired product.

Workup

  1. waitAfter 2 hours
  2. washwashed with saturated NH4Cl solution, saturated NaHCO3 solution and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (3% MeOH in methylene chloride)

Sources & evidence

ORD record
ord-8c4eb62e7f7444bf97be50908d1b79fa
Source dataset
uspto-grants-2012_01
Patent number
US08101639B2

Reaction notes

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