Hydrochloric Acid → 5-Acetyl-4-[(3,5-dichloropyridin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one

HRID 1725520

Reaction equation

HRID 1725520 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:9]([Cl:10])=[CH:8][N:7]=[CH:6][C:5]=1[Cl:11].[C:12]([C:15]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:19][N:18]([CH2:27][CH3:28])[C:17](=[O:29])[C:16]=1[N+]([O-])=O)(=[O:14])[CH3:13].Cl>C1COCC1.C(OCC)(=O)C>[C:12]([C:15]1[C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[N:19][N:18]([CH2:27][CH3:28])[C:17](=[O:29])[C:16]=1[NH:3][C:4]1[C:9]([Cl:10])=[CH:8][N:7]=[CH:6][C:5]=1[Cl:11])(=[O:14])[CH3:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 107320155-acetyl-2-ethylnitro6-phenylpyridazin-3(2H)-one

Product 1

HCID 671092825-Acetyl-4-[(3,5-dichloropyridin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-oneYield 16.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 50 mg (1.25 mmol) of sodium hydride in 5 ml of THF, 100 mg (0.62 mmol) of 4-amino-3,5-dichloropyridine in 5 ml of THF was added. The mixture was allowed stirring 30 minutes at room temperature and then cooled to 0° C. 150 mg (0.52 mmol) of 5-acetyl-2-ethyl-4-nitro-6-phenylpyridazin-3(2H)-one (Dal Piaz, V et al, J. Med. Chem. 1997, 40, 1417) in 10 ml of THF was added. The reaction was allowed to warm to room temperature and to continue stirring for 12 hours. The mixture was acidified with 2N HCl to pH 2. Ethyl acetate was added and the organic layer was washed with water, brine, dried over Na2SO4 anhydride and evaporated. The residue obtained (210 mg) was purified by column chromatography (silica gel, hexane/ethyl acetate 1:1) to yield the title compound (35 mg, 16.7% yield).

Workup

  1. additionwas added
  2. temperaturecooled to 0° C
  3. temperatureto warm to room temperature
  4. stirringto continue stirring for 12 hours
  5. washthe organic layer was washed with water, brine
  6. dry with materialdried over Na2SO4 anhydride
  7. customevaporated
  8. customThe residue obtained (210 mg)
  9. customwas purified by column chromatography (silica gel, hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-193fcd27e4d24c10aacff4977b15babe
Source dataset
uspto-grants-2009_02
Patent number
US07491722B2

Linked notes

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