Pyridinyl pyrimidines

The treatment of diethyl 7V-[2-(4-pyridinyl)pyrimidin-4-yl]aminomethy-lenemalonate with m-chloroperbenzoic acid (85%) in methylene chloride at 0°C for 1 hr, and then at ambient temperature for 16 hr, gave the N-oxide (1468) in 64% yield (77USP4018770, 77USP4032523). 

Different pyridinyl pyrimidines were prepared with Negishi couplings (Scheme 72). The reported procedure took advantage of the lower hygroscop-icity and higher solubility of zinc iodide in ethereal solvents, as compared... 

Scheme 72 Synthesis of a pyridinyl pyrimidine through a Negishi reaction...

Selective metalation of 2-fluoro-4-iodopyridine 91 followed by trapping with zinc chloride generated 92 that subsequently was reacted with 2,4-dichloropyrimidine to generate pyridinyl-pyrimidine 93 [33]. In addition to the standard reaction conditions, it was found that a microwave-assisted variation also provided the bis(heteroaryl) products in an efficient manner. 

Scheme 15.44. Synthesis of pyridinyl pyrimidines by the Negishi reaction.

Rosoxacin was obtained in 16% yield by the cyclization of isopropylidene N-ethyl-N-[3-(4-pyridinyl)phenyl]aminomethylenemalonate in pol-yphosphoric acid at 125-137°C for 30 min [77JAP(K)116460], Isopropylidene 2-pyridyl- and 2-quinolinylaminomethylenemalonates (1195) were cyclized in boiling phosphoryl chloride by the action of poly-phosphoric acid at I35-140°C. When the formation of hydrogen chloride gas ceased, the reaction mixtures were treated with an alcohol or water to afford the corresponding alkyl 4-oxopyrido[ 1,2-a]pyrimidine-3-carbox-ylates or alkyl 1 -oxopyrimido[ 1,2- ]quinoline-2-carboxylates (1196, R2 = alkyl) in 51-96% yields or to afford carboxylic acids (1196, R2 = H) in 64-84% yields (79MIP2 80MIP3 84S152). 

Although strictly speaking this example does not begin with a preformed ring, the explanation for the conversion of 236 into pyrrolo[3,2-tf pyrimidines 237 by heating with an amine appears to proceed via an unisolated pyrrole (Equation 84) <2000H(53)805>. This process can be explained by cyclization of 236 into 3-dimethylamino-4-(2-pyridinyl)pyrrole-2-carboxylate followed by reaction with another molecule of 236 in which the dimethylamino group is substituted by the aminopyrrole derivative. 

The treatment of Ar-(2-pyridinyl)acylacetamides 56 with P4SI0 gave 4-substituted 2//-pyrido[l,2-a]pyrimidine-2-thiones 57 in 28% yield [88JCS(D)433]. 

Pyridinyl)-3//-l,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one 313 has been shown to be a potent competitive antagonist of the AMPA subtype glutamate receptor. It may be useful as a neuroprotectant (95JMC587). 

Miesel (1976) obtained active analogues of diilubenzuron by repladng the /K hloroaniline moiety by substituted aminopyrazines. As an extension of their earlier work DeMilo et al. (1978) have synthesised and tested a series of new analogues where the aniline portion of the diilubenzuron molecule has been exchanged for various substituted heterocycles such as isoxazoles, thiazoles, thiadiazoles, pyridines, pyrimidines, 5-triazines and bicyclic heterocycles. The most active derivatives were the 4-bromo- (112) and 4-chloro-2-pyridinyl analogues (113) but none was as active as diilubenzuron. 

Pyrido[l,2-a]pyrimidinyl complexes can be prepared according to Scheme 26 [35]. The reaction of 43 with 2-aminopyridine gives a mixture of the pyridinium[l,2-a]pyrimidinyl compoimd [Ru(T)5-C5H5) 2,2-diphenyl-2//-pyridinium[l,2-a]pyrimidin-4-yl (CO)(P Pr3)]BF4 (90) and its azoniabutadienyl isomer [Ru(Ti5-C5H5) C(CH=CPh2)=NH(o-pyridinyl) (CO)(PiPr3)]BF4 (91). The molar ratio of the isomers in the mixture depends on the reaction temperature. At temperatures lower than -30 °C, isomer 90 is the main reaction product, while at 0 C an inverse relationship is observed. 

Mono- saccharide Phenyl- boronic acid 3-Carboxy- phenylboronic acid 3-Carboxy- benzoboroxole 3-Pyridinyl- boronic acid Pyrimidine- 5-boronic acid... 

Bonacorso HG, Bortolotto GP, Navaiini J, Porte LMF, Wiethan CW, Zanatta N, Martins MAP, Flores AFC (2010) Convergent procedure for the synthesis of trifluoromethyl-containing N-(pyridinyl-triazolyl)pyrimidin-2-amines. J Fluor Chem 131 1297-1301... 

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