C([O:3][C:4](=[O:21])[CH2:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)=[O:7])C.CO.C1COCC1.O[Li].O>O>[C:15]1([C:12]2[N:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[CH2:5][C:4]([OH:21])=[O:3])=[CH:14][CH:13]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1To a stirred solution of 5-amino-2-phenyl-pyridine (4.0 g, 0.0235 mol) in dichloromethane (40 mL) was added ethyl malonyl chloride (5.307 g, 0.035 mol) dropwise. The resulting mixture was stirred for 1 hour. The mixture was diluted with water and the product was extracted with dichloromethane. The organic layer was washed with saturated sodium bicarbonate solution, brine, dried over Na2SO4 and evaporated to afford 5.46 g (80%) of N-(6-phenyl-pyridin-3-yl)-malonamic acid ethyl ester. To a solution of N-(6-phenyl-pyridin-3-yl)-malonamic acid ethyl ester (5.46 g, 0.019 mol) in the mixture of methanol (27.5 mL), THF (55 mL) and H2O (16.5 mL) was added LiOH.H2O (1.212 g, 0.0288 mol). The resulting reaction mixture was stirred for 1 hour at ambient temperature then concentrated. The resulting residue was diluted with water, acidified with concentrated HCl and the product was extracted with ethyl acetate. The ethyl acetate was washed with brine, dried over Na2SO4 and evaporated under reduced pressure to afford 4.0 g (82%) of N-(6-phenyl-pyridin-3-yl)-malonamic acid.
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