Synthesis Involving Formation of Two Bonds

Condensation of an amidine with a 1,3-diketone is a popular method for the direct preparation of the six-membered-ring pyrimidine. Numerous methods exist for the synthesis of the prerequisite diketone and other dicarbonyl compounds, making this a very attractive strategy for the preparation of substituted pyrimidines. 

A method for the synthesis of 2-substituted pyrimidine-5-carboxylic esters is described based on the similar concept of condensation of amidine 

A flow process was reported for the synthesis of P-keto esters via the BF3 OEt2-catalyzed formal C-H insertion of ethyl diazoacetate into aldehydes.The P-keto esters were then condensed with a range of amidines to give a variety of 2,6-substituted pyrimidin-4-ols. The crude reaction mixture containing the P-keto esters was treacted with acetamidine hydrochloride, DBU, and EtOH to provide the corresponding pyrimidin-4-ol in excellent yields. 

Amidine addition to a,p-unsaturated carbonyl derivatives is another popular method to construct pyrimidine rings. 2,4,6-Tri(hetero)aryl-substituted pyrimidines can be readily synthesized in a three-component, one-pot process based upon a coupling-isomerization sequence of an 

Polysubstituted pyrimidines were synthesized from in situ generated a,p-unsaturated imines and the corresponding amidine or guanidine derivatives in a convenient one-pot procedure. It was proposed that the described transformations proceed via the initial formation of o,P-imsaturated imine that undergo nucleophilic attack by a bidentate nucleophile (amidine or guanidine). This step is then followed by elimination of ammonia and aromatization to yield the observed polysubstituted pyrimidine. 

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