3- Ethyl-2,6-dimethyl-47/-pyrido

The structures of hydroxylated metabolites of 3-ethyl-2,6-dimethyl-47/-pyrido[l, 2-a]pyrimidin-4-ones were determined on the basis of mass spectrometry and NMR spectroscopy (89MI13). 

The thermostability of the hydrochloride salt of 3-ethyl-2,6-dimethyl-4//-pyrido[l,2-a]pyrimidin-4-one (Chinoin-150) in aqueous solution was investigated (85MI4). Chinoin-150 was fairly stable in acidic medium, but a slow decomposition was observed at pH 7.4 and 9. At pH 12 nearly quantitative decomposition was detected after 11 days at 90°C. From the aqueous solution the ring-opened product 314 was isolated (87MI1). 

PPA and AcOH at 100 °C for 4 h gave 9-hydroxy-2,3-dimethyl-47/-pyrido-[1,2-a]pyrimidin-4-one in 24% yield (96EUP733633). Reaction of 2-aminopyridine and ethyl 2-acetoxyacetoacetate in boiling EtOH gave 2-methyl-3-hydroxy-4/7-pyrido[l,2-a]pyrimidin-4-one in 47% yield (94KFZ(10)23). 

Similar intermediates including o-ethoxycarbonyl-, o-cyano- and o-dimethyl-aminomethylene-piperidones or their imines have been used to give partially reduced analogues, e.g. (244), in the [2,3-. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

Ethyl (3S)-8-amino-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihy-dro-7//-pyrido[l,2,3- f< ]-l,4-benzothiazine-6-carboxylate was obtained by the reduction of the respective 8-nitro derivative (OOMIPIO). 

Oxidation of 7-hydroxy- and 7-aryl-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- f< ]-l,4-benzothiazine-6-carboxylates and 6-carboxamides with 3-chloroper-oxybenzoic acid in CH2CI2 yielded sulfoxides and sulfones, depending on the molar ratio of the substrate and oxidizing agent (00MIP7). A sulfoxide was prepared by the oxidation of ethyl (3S)-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7c]-l,4-benzothiazine-6-carbox-ylate (OOMIPIO). 

Shur and Israelstam carried out the cyclization of 2-pyridylaminomethy-lenemalonates (1001) in polyphosphoric acid at 110°C for 4 hr (68JOC3015). They reported that pyrido[ 1,2-a]pyrimidine-3-carboxylates (1002) were obtained, even if they started from A/-(6-methyl- or 4,6-dimethyl-2-pyri-dyl)aminomethylenemalonates (1001, R = Me, R1 = H, 4-Me). However, it was later demonstrated that, in the case of the 6-methyl derivative (1001, R = Me, R1 = H), instead of the pyrido[ 1,2-a]pyrimidine-3-carboxylate (1002, R = Me, R1 = H), the ethyl, hydrogen Al-(6-methyl-2-pyridyl)ami-nomethylenemalonate (378, R = Me) was probably obtained. The latter... 

Reaction of 2-ethoxy-3,3-dimethyl-3,4,6,7,8,9-hexahydro-2H-pyrido[2,l-6][l,3]oxazinium chloride with sodium ethylate, trimethylsilyl cyanide, or aqueous sodium bicarbonate yielded ring-opened products (91ZOB2743). 

The ethyl ester of l-cyclopropyl-7-(2,6-dimethyl-4-pyridyl)-5,6,8-trifluoro-4-oxo-1,4-di-hydroquinoline-3-carboxylic acid26 and of the closely related (7>)-10-(2,6-dimethyl-4-pyridyl)-8,9-difluoro-3-methyl-7-oxo-2.3-dihydro-7//-pyrido[1,2,3-tfe]-l,4-bcnzoxazine-6-carboxylic acid 427 can be thiolated in tetrahydrofuran at low temperature, using the strong base sodium hydride. 

Seidel28 cyclized compounds (32) derived from the amides (31) with dimethylformamide dimethyl acetal to the 3-substituted 2-oxo-2H-pyrido-[l,2- ]pyrimidines (33) by heating in acetic anhydride. On this basis he corrected the conclusion of Antaki,29 who had assumed that by reacting 2-amino-4-methylpyridine and ethyl ethoxymethylenecyanoacetate, the 2-oxo-2//-pyrido[l,2-a]pyrimidine (33 R = 8-Me, R1 = OEt) was produced. The product was in fact the 4-oxo isomer (36 R = 8-Me, R1 = H, R2 = COOEt). 

The product obtained from 2-aminopyridine and ethyl 2-methylaceto-acetate in ethyl polyphosphate was described by Mullock et al.6 as 1,8-naphthyridine, but it was shown later by Bowden and Brown82 to be 2.3-dimethyl-4-oxo-4/f-pyrido[l,2-n]pyrimidine (36 R1 = R2 = Me, R = H). 2-Acetylbutyrolactone (43) and its 5-substituted derivatives have also been used as )3-oxo ester component49-65-83 85. 

From 2-amino-6-methylpyridine and ethyl 3-aminocrotonate the expected 2,6-dimethyl-4-oxo-4//-pyrido[l,2-a]pyrimidine was not obtained, but instead a urea derivative is formed.36 Ethyl acetoacetate has also been replaced... 

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