Aldehydes are perennially attractive building blocks due to their ability to easily react with many nucleophiles. Recent work by Kiselyov describes a one-pot procedure to polysubstituted pyrimidines using various aldehydes (Scheme 1).1

Aldehydes

Scheme 1.

Collman has used 1-methylimidazole-5-carboxaldehyde in the synthesis of a functionalized tripodal ligand, which can serve as CuB site mimics of cytochrome c oxidase (Scheme 2).2 More recently, 1-methylimidazole-5-carboxaldehyde has been used in the synthesis of a series of tetrahydroquinoline analogues that show potent antimalarial activity (Scheme 3).3 Smith has used 1-methylpyrazole-4-carboxaldehyde to synthesize a series of orally active inhibitors of lipoprotein-associated phospholipase A2 (Scheme 4).4

Aldehydes

Scheme 2.

Aldehydes

Scheme 3.

Aldehydes

Scheme 4.

Highly substituted 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde has been of recent interest as well. One recent communication describes its use in the synthesis of an unnatural amino acid (ATPC) with promise in peptidomimetics.5 Another report uses 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde as a key building block in the synthesis of a crucial tricyclic intermediate for a series of new A3 adenosine antagonists (Scheme 5).6

Aldehydes

Scheme 5.

Materials
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1.
Kiselyov AS. 2005. One-pot synthesis of polysubstituted pyrimidines. Tetrahedron Letters. 46(10):1663-1665. http://dx.doi.org/10.1016/j.tetlet.2005.01.068
2.
Collman JP, Zhong M, Costanzo S, Zhang C. 2001. New Imidazole-Based Tripodal Ligands as CuBSite Mimics of CytochromecOxidase. J. Org. Chem.. 66(24):8252-8256. http://dx.doi.org/10.1021/jo010737m
3.
Nallan L, Bauer KD, Bendale P, Rivas K, Yokoyama K, Hornéy CP, Pendyala PR, Floyd D, Lombardo LJ, Williams DK, et al. 2005. Protein Farnesyltransferase Inhibitors Exhibit Potent Antimalarial Activity. J. Med. Chem.. 48(11):3704-3713. http://dx.doi.org/10.1021/jm0491039
4.
Boyd HF, Fell SC, Hickey DM, Ife RJ, Leach CA, Macphee CH, Milliner KJ, Pinto IL, Rawlings D, Smith SA, et al. 2002. Potent, orally active inhibitors of lipoprotein-associated phospholipase A2: 1-(biphenylmethylamidoalkyl)-pyrimidones. Bioorganic & Medicinal Chemistry Letters. 12(1):51-55. http://dx.doi.org/10.1016/s0960-894x(01)00678-3
5.
Varvounis G, Cordopatis P, Bissyris EE, Belekos D, Magafa V, Tsoungas PG. 2005. 2-Amino-4-pyrrolidinothieno[2,3-d]pyrimidine-6-carboxylic Acid as anN-Terminal Surrogate in Amino Acid and Peptide Analogues. Synthesis. 2005(18):3159-3166. http://dx.doi.org/10.1055/s-2005-918426
6.
Baraldi P. 2003. New strategies for the synthesis of A3 adenosine receptor antagonists. Bioorganic & Medicinal Chemistry. 11(19):4161-4169. http://dx.doi.org/10.1016/s0968-0896(03)00484-x