6.7.8.9- Tetrahydro-4H-pyrido

It is interesting that somewhat similarly 4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l, 2- ]pyrimidine (A) was transformed into 5,6,7,8-tetrahydro-l,8-naphthyridin-4(lH)-one (B) by action of sec-amines (79H1407). Also in this transformation bond-breaking occurs between the ring nitrogen and the carbon of the carboxyl group. 

Stirring a chloroform solution of 9a-amino-2-fm-butyl-4,6,7,8,9,9a-hexahy-dropyrido[2,l-b][l,3]thiazin-4-one at 35°C for 64 h afforded 2-tert-butyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-fl]pyrimidin-4-one in 95% yield [89JCS(P1)1231]. 

Syntheses starting from hydrogenated derivatives of 2-aminopyridines led to 4-oxo-6.7,8,9-tetrahydro-4H-pyrido[l,2-ci]pyrimidines. 

Attempts to reduce the quaternary salts of 4-oxo-4//-pyrido[l,2-a]-pyrimidines with sodium borohydride or lithium aluminum hydride remained unsuccessful.137 At the same time the 6,7,8,9-tetrahydro quaternary salts may readily be reduced with sodium borohydride to the 1-alkyl-l,6,7,8,9,9a-hexahydro derivatives.75-77,133 1481269 270 Sodium borohydride reduction of the 1,6- and l,7-dimethyl-3-carbamoyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidinium salts proceeds stereoselectively and yields the thermodynamically controlled product.271 The l-methyl-3-carbamoyl-4-oxo-l,6,7,8,9,9a-hexahydropyrido[l,2-a]pyrimidines were also prepared by the catalytic (Pd/C) hydrogenation of the 1,6,7,8-tetrahydro derivatives,270-272 but this reaction led to a diastereoisomeric mixture.271... 

Hydrolysis of the 9-ethoxymethylene derivatives in 0.5 N hydrochloric acid yielded the formyl compounds (241 R3 = H), which reacted with amines to provide the 9-aminomethylene derivatives (240). The 9-aminomethylene derivatives (240) were also prepared by reacting 4-oxo-6,7,8,9-tetrahydro-4H-pyrido [ 1,2-a]pyrimidines with N, N-dimethylformamide... 

The Ratio of E and Z Geometric Isomers of Ethyl 9-(Phenylhydrazono)- and 9-(Phenylamino)methylene-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[ 1, 2-a]pyrimidine-3-carboxylates (34, R1 = Ph R2 = H ... 

Cobalt-mediated C-H activation of pyrazone 287 with bis(trimethylsilyl) acetylene in the presence of cyclopentadienylcobaltbis(ethene) [CpCo (C2H4)2] afforded pyrido[l,2-a]pyrazin-4-one complex 288, and its decom-plexation with Fe3"" furnished 6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrazin-4-one 289 (07CEJ7443). 

If the reaction of 9-halo-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyri-midines and amines was carried out in the absence of air, the 9-amino-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidines were isolated, which could be oxidized by air to the 6,7-dihydro analogs. The latter were directly prepared from 9,9-dihalo-4-oxo-6,7,8,9-tetrahydro- or 9-hydroxy-4-oxo-6,7-dihydro-4/f-pyrido[l,2-a]pyrimidines ° with amines. 

Crystalline complexes were formed from ethyl 6-methyl-4-oxo-6,7.8.9-tetrahydro-4H-pyrido[1.2-u]pyrimidine-3-carboxylate and zinc chloride and from the quaternary salt (280) and mercuric potassium iodide. Optical resolution of 6-methyl-4-oxo-6,7,8.9-tetrahydro-4//-pyrido-[l,2-rt]pyrimidine-.3-carboxylic acid was carried out with the antipodes of... 

Hydrazono-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidines can also be prepared from 9-halo-,9,9-dihalo-6,7,8,9-tetrahydro-, and 9-hydroxy-6,7-dihydro-4H-pyrido[l,2-a]pyrimidines ° by treatment with hydrazines. 

In attempts to formylate the bicyclic compound 5-methyl-9-phenylhy-drazono-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2- z]pyrimidine 3-carboxy-late (129) with dimethylformamide-phosphoroxychloride at 90-100°C, a degenerate ring rearrangement took place, resulting in the formation of 7-(o -chloroethyl)-8-chloro-9-(A,A-dimethylaminomethylene)amino-6,7,8,9-tetrahydro-4-oxo-4H-pyrido[l,2-a]pyrimidine-3-carboxylate (131)... 

By hydrogenating 2.9-disubstituted 4-oxo-4H-pyrido[l,2-a]pyrimidines or their 6,7,8,9-tetrahydro derivatives over platinum(IV) oxide, Yale and Spitzmiller obtained a mixture of diastereomeric perhydro compounds.58 Separation was not attempted. 

The magnitudes of the coupling frequency of the 1,3-dicarbonyl moiety of 4-oxo-4H-, 6,7,8,9-tetrahydro-, l,6,7,8,9,9a-hexahydro-, and perhydro-4-oxo-4/f-pyrido[l,2-a]pyrimidine-3-carboxylates are characterized by shifts and by the intensity differences of the coupled vibration bands in their IR spectra (92MI11). 

Chemical Name 4H-Pyrido(l,2-a)pyrimidin-4-one, 6,7,8,9-tetrahydro-3-(2-(4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl)ethyl)-2-methyl-... 

Chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[l,2-a]pyrimidin-4-one monohydrochloride... 

A mixture of 5.3 parts of 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[l,2-a]pyrimidin-4-one monohydrochloride, 4.4 parts of 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole, 8 parts of sodium carbonate, 0.1 parts of potassium iodide and 90 parts of N,N- dimethylformamide was stirred overnight at 85°-90°C. After cooling the reaction mixture was poured into water. The product was filtered off and crystallized from a mixture of N,N-dimethylformamide and 2-propanol. The product was filtered off and dried, yielding 3.8 parts (46%) of 3-[2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl] ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[l,2-a]-pyrimidin- 4-one melting point 170°C. 

Tetrahydro-4-oxo-4H-pyrido[l,2-a]pyrimidines contain an active methylene group in position 9, which permits versatile transformations. " Depending on the molar ratio, halogenation of 4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2-fl]pyrimidines gave 9-halo or 9,9-dihalo com-pounds. " 9-Bromo- or 9-chloro-6-methyl-4-oxo-6,7,8,9-tetra-hydro-4H-pyrido[l,2-a]pyrimidine-3-carboxylic acids were obtained as 4 1 mixtures of the thermodynamically more stable 6,9-diaxial and the 6-axial, 9-equatorial-substituted diastereoisomers. ... 

Arylhydrazono derivatives may be prepared from 4-oxo-6,7,8,9-tetrahy-dro-4H- or 9-formyl-4-oxo-1,6,7,8-tetrahydro-4//-pyrido [ 1,2-a]pyrimidine with aryldiazonium salts.307... 

Preparation of 6-(2-chlorophenyl)-9-ethoxycarbonyl-l-methyl-7,8,9,10-tetrahydro-4H-pyrido[4, 3 4,5]thieno[3,2-f]-l,2,4-triazolo[4,3-a]-l,4-diazepine... 

---