4//-Pyrido pyrimidin -4-ones chromatography

Ferrarini et al. studied the reaction of 2,6-diamino- and 2-amino-6-acetamidopyridine with different jS-oxo esters in polyphosphoric acid at 80°C (90JHC881). Generally, complex reaction mixtures that contained different bi- and tricyclic products were obtained (see Scheme 7 and Table IX). The products were separated by flash chromatography. In the case of 2-amino-6-acetamidopyridine, the 2,6-diacetamidopyridine 97 was the main product. This compound 97 was also obtained by transamidation in good yield when 2-amino-6-acetamidopyridine was heated in polyphosphoric acid at 80°C. 2-Hydroxy-1,8-naphthyridines 98 were formed in a Conrad-Limpach-type cyclocondensation of 2-aminopyridines and /3-keto ester, while 4-hydroxy-1,8-naphthyridines 99 were probably formed by a ring transformation of 4//-pyrido[l,2-a]pyrimidin-4-ones 100 obtained by the cyclocondensation of 2-aminopyridines and a /3-keto ester. The cyclocondensation of 7-amino-4-hydroxy-l,8-naphthyridine 99 (R = H) and a... 

Hydroxyethyl)pyrido[l,2-a]pyrimidin-4-one 104 was prepared by the ring closure of 2(3//>furanone 103 in 1,2-dichloroethane in the presence of aluminum trichloride at 80°C for 0.5 hour in 54% yield after column chromatography (91EUP453042). 

Nitro-4-oxo-l, 6,7,8-tetrahydro-4/f-pyrido[l, 2-a]pyrimidines 534 (R = 6-, 7-, and 8-Me) or 538 were also obtained from 9-formyl-4-oxo-1,6,7,8-tetrahydro-4i/-pyrido[l,2-a]pyrimidine-3-carboxylates 536 with Clayfen in 24-54% yields (90JOC6198), or from 9-bromo-6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 537 with sodium nitrite in 40-62% yields (87H869). From the reaction mixture of 9-formyl-6-methyltetrahydropyridopyrimidine-3-carboxylate 536 (R = 6-Me) both 32% of 9-nitro derivative 534 (R = 6-Me) and 5% of dinitro compound 535 (R = Me) were isolated following column chromatography (90JOC6198). 

Aminopyridine was treated with sodium hydride in tetrahydrofuran at room temperature for 1 hour then 6-chloro-l,3-dipropylpyrimidinedi-one 697 was added to the reaction mixture, which was stirred overnight at room temperature (94JHC81). After work-up and chromatography, 6-(2-pyridyl)aminopyrimidinedione 698 and 2//-pyrido[l,2-a]pyrimidin-2-one 699 were obtained in 34% and 12% yield, respectively. In the case of 2-amino-5-chloropyridine, the appropriate pyrimidinedione was obtained in 62% yield. 

A mixture of 3-(2-bromoethyl)-2-methyl-pyrido[l,2-a]pyrimidin-4-one monohydrobromide, 3-furan-2-yl-methyl-(3H-imidazo[4,5-b]pyridine-2yl)-4-piperidinyl)-amine dihydrobromide, of sodium carbonate and of N,N-dimethylformamide was stirred and heated overnight at about 70°C. The reaction mixture was poured onto water. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (94 6 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 3-(2-(4-((3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-yl)amino)-l-piperidinyl)ethyl)-2-methyl-4H-pyrido[l,2-a]pyrimidin-4-one melting point 202°C. 

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