C[O-].[Na+].C([CH:6](CC)[C:7]([NH:9][CH:10]([C:14]([O-])=O)[C:11]([O-:13])=[O:12])=[O:8])C.Cl.ClC[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[OH-].[Na+]>CO.O>[C:7]([NH:9][CH:10]([C:11]([OH:13])=[O:12])[CH2:14][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)(=[O:8])[CH3:6]
A solution of sodium methoxide (65.8 g, 1.22 mol) in methanol (300 ml) was treated portionwise with diethylacetamidomalonate (132.3 g, 0.61 mol) maintaining a temperature of ca. 45° C. The mixture was then heated under reflux for 15 min. The mixture was cooled to 50° C. then treated slowly with a suspension of 2-chloromethylpyridine hydrochloride (100 g, 0.61 mol), the pink suspension was then heated under reflux for a further 6 h. Water (500 ml) was added followed by 10M sodium hydroxide (122 ml, 1.22 mol) and the pH was maintained at ca. 11 while heating the mixture at 70° C. overnight. The mixture was cooled to RT and the methanol removed in vacuo. The aqueous residue was washed with ethyl acetate (2×500 ml), then acidified to pH 5 and further washed with ethyl acetate (2×500 ml), before evaporating in vacuo to provide a semi-solid. The residue was triturated with hot ethanol (500 ml) and the sodium chloride removed by filtration. The filtrate was then evaporated in vacuo and the residue crystallised from methanol-ethyl acetate to provide the title compound (70 g, 66%) as a yellow solid.
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