9-Amino-6,7-dihydro-4//-pyrido pyrimidin-4-ones

The starting material is produced by reacting 6-amino-2-methylthiopyrimidine with ethoxymethylene malonic acid diethyl ester. That intermediate is thermally treated in diphenyl ether to give 6-ethoxycarbonyl-2-methylthio-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine. The ethoxy group is hydrolyzed off with sodium hydroxide and one nitrogen is ethylated with diethyl sulfate to give the starting material. These are the same initial steps as used in the pipemidic acid syntheses earlier in this volume. 

Heating 9-hydrazono-6,7,8,9-tetrahydro-47/-pyrido[l,2-a]pyrimidin-4-ones 291 in a mixture of POCI3 and DMF at 95 °C gave 8-chloro-7-(chloromethyl)-9-[(dimethylaminomethylene)amino-477-pyrido[l,2-a] pyrimidin-4-ones 293 via 9-hydrazino-6,7-dihydro-477 derivatives 292. At lower temperature 9-[(dimethylaminomethylene)amino]-7-dimethylami-nomethylene-8-chloro-6,7-dihydro-477-pyrido[ 1,2-a]pyrimidin-4-ones 294... 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

Amino-6,7-dihydro-4//-pyrido[l,2-a]pyrimidines 596 were prepared from 9-bromotetrahydropyridopyrimidin-4-ones 592 with sodium azide in acetone at 25°C in 42-55% yields (85TL3621). Considering the very mild reaction conditions, a cyclic intermediate 595 was suggested instead of a nitrene intermediate. 

Ring transformation of the initial 6-substituted 4//-pyrido[l,2-a] pyrimidin-4-ones also occurred when 2-[(6-substituted 2-pyridyl)acrylates were heated in a high-boiling solvent. For example, heating diethyl [(4,6-dimethyl-2-pyridyl)amino]malonate in boiling diphenyl ether afforded ethyl 5,7-dimethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate... 

Reaction of 8-amino-7-cyano-2,6-dihydro-lH-pyrido[l,2-c]pyrimidin-1-one 76 and H2NNH2 H20 afforded tricyclic derivative 77 (08H(75)887). 

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l,2-a]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-l,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4/7-pyrido[l,2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-1,4-dihydro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

---