1-[4-(Benzyloxy)-2-fluorophenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-[4-(benzyloxy)-2-fluorophenyl]-5-methoxypyridazin-4(1H)-one

HRID 1895158Notes

Reaction equation

HRID 1895158 reaction equation
[CH3:1][Mg+].[Br-].[CH2:4]([O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH:23]=[C:22]([O:24][CH3:25])[C:21](=[O:26])[C:20]([C:27](N(OC)C)=[O:28])=[N:19]2)=[C:14]([F:33])[CH:13]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C1COCC1>[C:27]([C:20]1[C:21](=[O:26])[C:22]([O:24][CH3:25])=[CH:23][N:18]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[CH:13][C:14]=2[F:33])[N:19]=1)(=[O:28])[CH3:1]

Participants

4

Reactant 2

HCID 866439351-[4-(Benzyloxy)-2-fluorophenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound

Product 1

HCID 594362803-Acetyl-1-[4-(benzyloxy)-2-fluorophenyl]-5-methoxypyridazin-4(1H)-oneYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

MeMgBr (1 M solution in THF, 56.4 mL, 56.4 mmol) was added dropwise at −78° C. to a solution of 1-[4-(benzyloxy)-2-fluorophenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (7.77 g, 18.8 mmol) in THF (120 mL). After stirring for 1 h, the reaction mixture was quenched with 1 M HCl aqueous solution and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with AcOEt and crystallized from hexane/AcOEt to give the title compound (5.86 g, 85% yield) as a pale yellow solid: mp 101-103° C.; 1H NMR (300 MHz, CDCl3): δ ppm 2.67 (3H, s), 3.89 (3H, s), 5.13 (2H, s), 6.84-6.93 (2H, m), 7.34-7.44 (5H, m), 7.48-7.55 (1H, m), 7.69 (1H, d, J=2.3 Hz). Anal. Calcd for C20H17FN2O4: C, 65.21; H, 4.65; N, 7.60. Found: C, 65.37; H, 4.68; N, 7.47.

Workup

  1. customthe reaction mixture was quenched with 1 M HCl aqueous solution
  2. extractionextracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with AcOEt
  8. customcrystallized from hexane/AcOEt

Sources & evidence

ORD record
ord-0edeba24f46f4b00932c531117eb8ed7
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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