6,7-Disubstituted pyrido

Aminopyrimidine-5-carboxaldehyde 284 with aromatic ketomethy-lenes provides 7- and 6,7-disubstituted pyrido[2,3-d]pyrimidines 285. Facile ring opening of the pyrimidine moiety of this heterocyclic system gives substituted 2-aminonicotinaldehydes 286 (Scheme 62) (75J(3C1438). 

A series of 2,3-disubstituted pyrido[4,3-d]pyriinidin-4(3Zf)-ones (154) showed more complicated fragmentation patterns. Here again, however, strong molecular ions were invariably present and m/2e peaks were common, as were M-1 peaks. The nature of the group Rj... 

Disubstituted pyrido[3,4- ]pytazines 90 were reacted with equivalent amounts of trimethylsilyl cyanide and acyl chlorides or chloroformates in the presence of a catalytic amount of AICI3 in CH2CI2 to give the Reissert compounds 91, where the reactions occurred across the C-5,N-6 bond <1994JHC819>. On the other hand, treatment of 90 (R = = Ph) with benzenesulfonyl chloride and trimethylsilyl cyanide in the presence of a catalytic amount of... 

Reaction of 1,3-diketones and 2-aminopyridines led to 2,4-disubstituted pyrido[l,2-a]pyrimidinium salts (6 R1 and R2 H), but the 6-substituted 2-aminopyridine failed to provide the bicyclic product.4,5 The irregular behavior of the 6-substituted 2-aminopyridines is explained by the steric hindrance effect of the 6-substituent. 

Ring closure proceeded with 2,6-diaminopyridine, but instead of the 6-amino-2,4-disubstituted-pyrido[l,2-c<]pyrimidinium salts, 2-amino-5,7-di-substituted-l,8-naphthyridines were formed.4,11... 

With aryldiazonium chlorides the pyrido[l,2-a]pyrimidines (63 R = H) yielded the 3-arylazo derivatives.253 The 3-methyl derivative of 63 (R = H) was also subjected to diazo coupling, but the product, a 3,3-disubstituted pyrido[l,2-a]pyrimidine, underwent immediate transformation involving hydrolysis of the C-4—N-5 bond253 (see also Section III.C,4). 

A series of 2,7-disubstituted pyrido[3,2- ]quinolines (24) were obtained by a double Friedlander reaction on 4,6-diamino-isophthalaldehyde (Equation (10)) <84LA133>. 

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

Various diethyl 6-aryl- and 6-aryl-2-methylpyridine-3,4-dicarboxylates can be treated with hydrazine in refluxing ethanol to give products in the form of the hydrazinium salts of the corresponding 7-substituted and 5,7-disubstituted pyrido[3,4-<7]pyridazine-l,4(2//,3//)-diones 6 NH2NH2, which can be converted into the free compounds by acetic acid.119-121... 

Substituted or 5,7-Disubstituted Pyrido[3,4-(/ pyridazine-l,4(2//,3//)-diones 6 General Procedure 119... 

Suitable cyclization partners are 2-(acylamino)nicotinic acids and primary amines, giving 2,3-disubstituted pyrido[2,3-r7]pyriinidin-4(3//)-ones. Thus, 3-aryl-2-methylpyrido[2,3-c/]pyrimidin-4(3/f)-ones 22 are synthesized by fusion of 2-acetamidonicotinic acid with arylamines.33... 

Besides ring contraction to give 177-imidazo[4,5-A]pyridines 3 (cf. Section 7.2.3.1.2.1.), several 6-halo-2,3-disubstituted pyrido[2,3-A]pyrazines 1 undergo dehalogenation on treatment with potassium amide in liquid ammonia to yield pyrido[2,3-A]pyrazines 2.34... 

Various 1,5-diketones of type 30 have been cyclized using ammonium acetate in acetic acid to give 1,3-disubstituted pyrido[l,2-a]pyrazinium salts (31). Similar treatment of the ester 32 gave the oxo compound 33. 

Narsaiah and co-workers employed the Dimroth rearrangement in their preparation of novel 4-substituted-amino-5-trifluormethyl-2,7-disubstituted pyrido[2,3-< pyrimidines and evaluated their potential as antibiotics against Gram-positive and Gram-negative bacteria. Treatment of iminoether 121 with methyl amine in ethanol at room temperature for 3 h gave rise to 7V-methyl-2-methyl-7-phenyl-5-(trifluoromethyl)pyrido[2,3-i/)pyrimidin-4-amine 122 in 84% yield. This compound showed significant... 

Included among the various antimalarlal compounds synthesized >dilch show activity in mice are 6,8-disubstituted pyrido [2,3-b] pyrazines, mono- and di-sydnone derivatives of DDS, 9 90 3 phenylrhodanines,91... 

The syntheses of pyrido[3,2-d]pyrimidines from pyridines utilize a 2,3-disubstituted pjrridine and insert the C-2 and N-3 atoms, either previously linked (route i) or in separate stages (route ii). 

This is the least investigated system and the few known derivatives have been synthesized from 3,4-disubstituted pyridines (routes i or ii). The first recorded pyridopyrimidine of any system was pyrido[3,4-d]-... 

Amino-4//-pyrido[],2-rz]pyrimidin-4-ones 184 were obtained from 3-(2,2-disubstituted ethenylamino) derivatives 183 with H2NNH2 H2O or HONH2 HCI m good yields, and from 183 (R = COOCH2Ph, R = acetyl) by treatment with NaBH4 in moderate yields (97H(45)2349,... 

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