4-Acetylpyridine → Diethyl hydroxy[2-oxo-2-(4-pyridinyl)ethyl]propanedioate
Reaction equation
[O:1]=[C:2]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:13]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)(=[O:15])[CH3:14]>>[OH:1][C:2]([CH2:14][C:13]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)=[O:15])([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:8]([O:10][CH2:11][CH3:12])=[O:9]Participants
Procedure
Diethyl ketomalonate (17.4 g, 0.1 mol) was heated with 4-acetylpyridine (12.1 g, 0.1 mol) at 120° C. for 15 h under nitrogen to provide diethyl 2-hydroxy-2-(4-pyridyl)cabonylmethyl-malonate as a crystalline solid. The diester was refluxed in ethanol with a slight excess of hydrazine hydrate hydrochloride for 15 h to provide 3-hydroxy-6-(4-pyridyl)-4-carbethoxy-pyridazine (4, Scheme 1). The above ester was recrystallized from ethanol, hydrolyzed with aqueous sodium hydroxide followed by careful neutralization with hydrochloric acid to afford 3-hydroxy-6-(4-pyridyl)-pyridazine-4-carboxylic acid (5, Scheme 1). The acid was dissolved in phosphorous oxychloride containing a catalytic amount of DMF and the mixture was allowed to react at 80° C. for 4 h to provide 3-chloro-4-chlorocarbonyl-6-(4-pyridyl)pyridazine (6, Scheme 1) as a dark oil The above dichloride was treated with gaseous ammonia in acetonitrile to afford the title compound as a tan solid. The above dichloride was treated with excess gaseous ammonia to afford the title compound as a tan solid: 1H NMR (DMSO-d6) δ 8.80 (d, J=6 Hz, 2H), 8.59 (s, 1H), 8.20 (s, 1H), 8.17 (d, 6 Hz, 1H).
Sources & evidence
- ORD record
- ord-2d5c4898aadd49879dbd5416034d7ffa
- Source dataset
- uspto-grants-2000_09
- Patent number
- US06121266
Reaction notes
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