Diphenyl substituted 5-pyrimidine

Table IV. Comparative Activity of Substituted Diphenyl-5-pyrimidine Methanols...

The cyclization of educts with a C-C-C—N pyrimidine structure is similar to the second step of the Gould-Jacobs reaction.194 The reaction of an appropriately substituted pyrimidin-4-amine with diethyl (ethoxymethylene)malonate affords the requisite diethyl [(pyrimidinyl-amino)methylene]malonate. The thermal cyclization of this intermediate, an acylation of the pyrimidine nucleus by one of the ester functions to give ethyl 5-oxopyrido[2,3-t/]pyrimidine-6-carboxylate 1, is effected by heating to 250-320 °C, preferably in mineral oil,195 Dowtherm,196 or diphenyl ether.197 201... 

Reactions with methylphenylcyclopropenone (154) provided an opportunity to compare the reactivities of the two different C—CO bonds. The reaction of 2-aminopyridines with methylphenylcyclopropenone (154) proceeded more slowly than with the diphenyl analog (153). In ether, formation of the ds-2-oxopyrido[l,2-a]pyrimidines (158 R1 = Me) and/or the imidazo[l,2-c<]pyridines (162) was observed, indicating that the cycloaddition proceeds via cleavage of the PhC—CO bond. The methyl-substituted trans-2-oxopyrido[l,2-a]pyrimidine (160 R1 = Me) was only detected in the reaction mixture of 2-amino-3-methylpyridine, where the H NMR spectrum exhibited signals assigned to 160 (R1 = Me, R = 9-Me). The compound was not isolated. The imidazo[l,2-a]pyridines (162) readily hydrolyzed to the acids (163), work-up therefore leading mainly to isolation of the acids. 

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... 

There are a series of communications about the formation of dihydroazines by direct reaction of urea-like compounds with synthetic precursors of unsaturated carbonyls—ketones, containing an activated methyl or methylene group. The reaction products formed in this case are usually identical to the heterocycles obtained in reactions of the same binuclephiles with a,(3-unsatu-rated ketones. For example, interaction of 2 equiv of acetophenone 103 with urea under acidic catalysis yielded 6-methyl-4,6-diphenyl-2-oxi- 1,6-dihydro-pyrimidine 106 and two products of the self-condensation of acetophenone— dipnone 104 and 1,3,5-triphenylbenzene 105 [100] (Scheme 3.32). When urea was absent from the reaction mixture or substituted with 1,3-dimethylurea, the only isolated product was dipnon 104. In addition, ketone 104 and urea in a multicomponent reaction form the same pyrimidine derivative 106. All these facts suggest mechanism for the heterocyclization shown in Scheme 3.32. 

In a series of 2,7-diphenyl 5-substituted pyrido[4,3-d]pyrimidines (155, R = OH, OEt, Cl, SH, NHNH2) the molecular ions and peaks for the expected phenyl degradation at 65, 63, 52, 51, 50, and 39 were all generally strong. Here again peaks were visible for m/2e ions and for M-l and PhCN ions. The variations in the group R affected the breakdown pattern, but ions for m/e = 282 (156) and m/e= 152 (157) were common. 

Upon heating in Dowtherm [a mixture of biphenyl (26.5%) and diphenyl ether (73.5%)], some 4-(acylamino)pyrimidine-5-carboxamides 3 furnish 2-substituted pyrimido[4,5-cf]pyrimidin-4-ols 4.118... 

Triphenyl-l,3,5-oxadiazinium pentachlorostannates (71 X = SnCl5) are reported to react with primary enamines in boiling acetonitrile to yield 5-substituted 2,4-diphenyl-6-methyl-pyrimidines (72 R = C02Et, 80% R = COMe, 60%) (Scheme 8) <92CHE1054>. 

Treatment of 2-aminopyrazine with esters of ethoxymethylenemalonic acid gives the substituted amino compounds 9, which may be cyclized to 4-oxopyrazino[l,2-a]pyrimidines by heating in diphenyl ether at 250°. When the diethyl ester 9 (R = = Et) is cyclized, the 3-ethoxycarbonyl... 

---