3.4- Dihydro-2//-pyrido pyrimidines

Quiroga, J., Cisnero, C., Insuasty, B., Abonia, R., Nogueras, M. and Sanchez, A., A regiospecific three-component one-step cyclocondensation to 6-cyano-5, 8-dihydro pyrido [2,3-d]pyrimidin-4-(3H) ones using microwaves and solvent-free conditions, Tetrahedron Lett., 2001, 42, 5625-5627. 

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. 

Piromidic acid (PA), 5,8-dihydro-8-ethyl-5-pyrrolidopyrido(2,3-carboxylic acid is a pyrido pyrimidine derivative, a congener of nalidixic acid. PA is widely used for its antibacterial activity against several gram negative pathogens. PA is very slightly water soluble [4, 5]. 

The corresponding saturated dialkylamino ketones (Mannich bases) have also been used to provide 5,6-dihydro derivatives, which are oxidized in air to aromatic pyrido[2,3-[Pg.229]

H,4H-Oxazolo[5,4,3-y]pyrido[3,2-g]quinolin-4-one, 8-hydroxymethyl-6-methyl — see Nybomyein 5H-Oxazolo[2,3-[Pg.731]

Pyrido[2,3-(i]pyrimidine, 6-cyano-O-tosylation, 3, 211 Pyrido[2,3-(i]pyrimidine, 3,4-dihydro-synthesis, 3, 217... 

Polymorphic forms of I and II of 3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-3,6-dihydro-2//-pyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido [1,2-n]pyrimidin-4-one was characterized by IR spectroscopy (99MIP1). 

Heating 9-ethoxycarbonylmethylene-4-oxo-6,7,8,9-tetrahydro-4//-pyrido-[l,2-n]pyrimidine-3-carboxylate (157) at 250°C yielded 6,7-dihydro derivative 158 (99T10221). Under similar conditions 9-benzylidene-6,7,8,9-tetrahydro derivatives 159 did not gave the respective 9-benzyl-6,7-dihydro isomer. 

Photolytic cleavage of the substituent in position 1 of 1,2-dihydro-6//-pyrido[],2-n]pyrimidine-2,6-dione 160 with 320nm light gave 6//-pyr-ido[],2-n]pyrimidm-6-one 161 (95MIP1, 96MIP4, 96USP5580872). 

Cyclization of 3-cyano-2-[(3-hydroxypropyl)amino]-5-(4-pyridyl)pyri-dine-l -oxide (298) in POCI3 yielded 9-cyano-7-(4-pyridyl)-3,4-dihydro-2/f-pyrido[],2-n]-pyrimidine I -oxide (299) (94EJM175). After heating 3-cyano-4-trifluoromethyl-6-phenyl-2-[(3-hydroxypropyl- and 3-hydroxybutyl)-amino] pyridines in boiling POCI3 for 1 h, the product was treated with aqueous NH4OH to yield 6-phenyl-8-trifluoromethyl-9-cyano-3,4-dihydro-2//-pyr-ido-[l,2-n]pyrimidine and its 4-methyl derivative (01CHE329). 

Heating diethyl (2-pyridylamino)methylenemalonates 304 (R = COOEt, = Me, OH) in AcOH afforded 4-oxo-4//-pyrido[l, 2-n]pyrimidine-3-carboxylates 305 (R = Me, OH) (96JHC1041). Flash vacuum thermolysis of 2-substituted 3-(2-pyridylamino)acrylates 304 (R = CN, COOEt, R = H) through a packed silica tube (530 °C, 0.01 mmHg) gave 3-substituted 4//-pyrido[l,2-n]pyrimidm-4-ones 306 (R = CN, COOEt) (94AJC1263). Ethyl 7-methyl-4-oxo-l, 4-dihydro-1,8-naphthyridine-3-carboxylate (79%) was... 

Dodecyloxy-3-(2-chloroethyl)-2-methyl-4//-pyrido[l,2-n]pyrimidin-4-one 317 was obtained by cyclization of 3- l-[(3-dodecyloxy-2-pyridyl)ami-no]ethylidene -4,5-dihydro-2(3//)-furanone (316) in boiling POCI3 (95MIP4). 

Reaction of 2-(arylmethyleneamino)pyridines 335 and styrenes in the presence of hydroquinone afforded 2,4-diaryl-3,4-dihydro-2/f-pyrido[l,2-n]pyrimidines 336 by means of an inverse electron demand Diels-Alder reaction (95MI10). Reaction of 2-(benzylideneamino)pyridines 337 and chloroacetyl chloride gave 2-aryl-4//-pyrido[l,2-n]pyrimidin-4-ones 338 (97JMC2266). 

Heating the crystalline salt 2-aminopyridinium propiolate (346) at 100 °C in the solid state led to a 10 9 mixture of 2/f-pyrido[l,2-n]pyrimidin-2-one and ( )-3-(2-imino-l,2-dihydro-l-pyridyl)acrylic acid (347). Analysis of differental scanning calorimetry data shows unambiguously that the reaction takes place in the solid state. An endothermic peak at 81.1 °C corresponds to a solid state reaction, and a peak at 122-123 °C is attributed to melting. The product ratio of 2//-pyrido[l, 2-n]pyrimidin-2-one and 347 is 1 2.5 at 60°C, and 1 1.4 at 80°C (94MI12). 

Dihydro-2//-pyrido[l,2-n]pyrimidin-2-one was used in the synthesis of antiallergic tricyclic triazolobenzazepine derivatives (99MIP3). 8-[2-(4-f-Propyl-2-thienyl)ethenyl]- and 8-[(4-/-propryl-2-thienyl)methoxy]-4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxylic acids were patented for the treatment of preventing and/or treating microbial infectious diseases (OlMIPl). 

Among other bicyclic amidine catalysts, 3,4,6,7,8,9-hexahydro-2//-pyrido[l,2-n]pyrimidine was also applied in the preparation of /3-alkoxy nitriles from Q ,/3-unsaturated nitriles and alcohols (99GEP 19803515). The azido group could be smoothly converted into a trifluoroacetylamido group by treatment with (Cp3CO)2 in the presence of Ph3P and 2,3-dihydro-2//-pyrido[l,2-n]pyrimidin-2-one under Ar in THE (99HCA2380). 

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). 

Reaction of 7-bromo-4-(2,6-dichlorophenyl)-l,2-dihydro-3//-pyrido[l,2-c]pyrimidin-3-one (146) and PhSH in boiling xylene in the presence of Bu3SnOMe and (Ph3P)4Pd gave 7-(phenylthio) derivative in 52% yield (98MIP11, 00USP6147080). 

Treatment of pyrimidine-2-thione 193 with AICI3 in PhN02 yielded 2-(4-benzylphenyl)-6-oxo-6,7-dihydro-4//-pyrido[6,l-a]isoquinolin-4-thione (194) (98MI47). Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquina-zoline-2,4-dione (195) in PPA afforded l,2,3,5,6,7-hexahydropyrimido[3,2, l-//]quinazoline-l,3,7-trione (196) (97CHE96). 

Cyclocondensation of a-aryl-2-pyridylacetamides and 2-(3,4-dihydroiso-quinolin-l-yl)acetamide with Et2C03 in the presence of NaOEt in boiling EtOH afforded 4-aryl-2,3-dihydro-l//-pyrido[l,2-c]pyrimidine-l,3-diones (99JHC389) and 6,7-dihydro-4//-pyrimido[6,1 -a]isoquinoline-2,4-dione (98MIP15), respectively. 

Hydrazone of 1 -hydrazino-1 -hydroxy-4-phenyl-1,2-dihydro-3//-pyrido [l,2-c]pyrimidin-3-one was patented as cross-linkers for making physiologically compatible and H2O insoluble hydrazine or hydrazono compounds (97JAP(K)97/59303). 

Chemical Name 8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido[2,3-d] pyrimidine-6-carboxylic acid... 

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