Hydrochloric Acid → 5-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

HRID 422832Notes

Reaction equation

HRID 422832 reaction equation
[F:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[C:5]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][C:12]=2[F:19])=[C:4]([C:20]([NH:22][O:23][CH2:24][CH2:25][O:26]C=C)=[O:21])[CH:3]=1.Cl.[OH-].[Na+]>CCO.CCOC(C)=O.O>[F:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[C:5]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][C:12]=2[F:19])=[C:4]([C:20]([NH:22][O:23][CH2:24][CH2:25][OH:26])=[O:21])[CH:3]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 866125345-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide

Product 1

HCID 166666515-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamideYield 70%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide (0.121 g, 0.294 mmol) in EtOH (3 mL) was added 2 M HCl (0.75 mL). The reaction mixture was stirred at room temperature for 16 hours. The pH of the reaction mixture was adjusted to pH 7 with 1 M NaOH. The reaction mixture was diluted with EtOAc and H2O. The organic layer was separated and washed with saturated NaCl. The combined aqueous layers were back extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by silica gel flash column chromatography (methylene chloride/MeOH, 15:1) gave 5-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide (0.079 g; 70% over two steps) as a white solid. MS ESI (+) m/z 386 (M+1) pattern detected; 1H NMR (400 MHz, DMSO-d6) δ 11.54 (br s, 1H), 9.65 (br s, 1H), 7.65 (d, 1H), 7.23 (dd, 1H), 6.99 (dd, 1H), 6.81 (t, 1H), 4.67 (t, 1H), 3.74 (t, 2H), 3.51 (q, 2H), 3.25 (s, 3H), 2.46 (s, 3H).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated NaCl
  3. extractionThe combined aqueous layers were back extracted with EtOAc (1×)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel flash column chromatography (methylene chloride/MeOH, 15:1)

Sources & evidence

ORD record
ord-f08161dad4f044e4aeb723453562ef3c
Source dataset
uspto-grants-2012_01
Patent number
US08101639B2

Reaction notes

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