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

HRID 15961Notes

Reaction equation

HRID 15961 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([C:19]([NH:21][O:22][CH2:23][CH2:24][O:25]C=C)=[O:20])=[N:13][N:14]([CH3:18])[C:15](=[O:17])[CH:16]=1.Cl>CCO.C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([C:19]([NH:21][O:22][CH2:23][CH2:24][OH:25])=[O:20])=[N:13][N:14]([CH3:18])[C:15](=[O:17])[CH:16]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 866016154-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridazine-3-carboxamide

Product 1

HCID 166671574-(2-fluoro-4-(methylthio)phenylamino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamideYield 22%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a solution of 4-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridazine-3-carboxamide (30 mg, 0.077 mmol) in EtOH/THF (2 mL/2 mL) was added 1 N aqueous HCl (0.15 mL, 0.15 mmol, 1 N aqueous solution) at room temperature. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was neutralized to pH 7, diluted with EtOAc (3×), washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (100% EtOAc to 100% CH2Cl2 to 2.5 to 3 to 5% MeOH in CH2Cl2) to afford 6 mg (22%) of the desired product. MS APCI (−) m/z 367 (M−1) detected; −1H NMR (400 MHz, CD3OD) δ 7.35 (t, 1H), 7.18 (dd, 1H), 7.14 (dd, 1H), 5.92 (s, 1H), 4.06 (t, 2H), 3.79 (t, 2H), 3.74 (s, 3H), 2.51 (s, 3H).

Workup

  1. washwashed with water
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude material that
  6. customwas purified by silica gel flash column chromatography (100% EtOAc to 100% CH2Cl2 to 2.5 to 3 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-6061cc9a1b97426f8a83cba59ce8f5cc
Source dataset
uspto-grants-2010_06
Patent number
US07732616B2

Reaction notes

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