Pyrimidine-5-carboxaldehyde

Pyrimidine-5-carboxaldehyde is used in the preparation of (S)- and (R)-pyrimidyl alkanol by reacting with diisopropylzinc and (n-butyl)ethyl(n-hexyl)(n-propyl)methane.

Pyrimidine-5-carboxaldehyde serves as a reagent for synthesizing (E)-2-Carbamoyl-1-(naphthalene-2-yl)-3-(pyrimidin-5-yl)prop-2-en-1-one and modifying ring B structures by incorporating different pyridines[6]. The compound reacts with diisopropylzinc under asymmetric autocatalysis to produce optically active pyrimidyl alkanol[7].

Under nitrogen, a solution of 5-bromopyrimidine (1 g, 6.3 mmol) in 60 mL anhydrous THF was added BuLi (2.5 M, 2.6 mL, 6.5 mmol) at -78° C. The resulting yellow solution was stirred for 20 min, after which ethyl formate (0.55 mL, 6.7 mmol) was added dropwise over 5 min. After 20 min, the reaction was quenched with 1.5 M THF/HCl solution (4.5 mL, 6.7 mmol). The cold bath was removed, and the reaction mixture was stirred for 1 h. THF was removed in vacco, 10 mL of water was then added. The mixture was extracted with CHCl3 (2*10 mL), and the combined organics were dried (MgSO4) and concentrated. The crude product was purified via flash column chromatography (5 per cent MeOH/CHCl3) to give 0.35 g (51 per cent) of the titled Pyrimidine-5-carboxaldehyde.

[1] Journal of medicinal chemistry,  2004,  vol. 47,  # 20,  p. 4829 - 4837
[2] Patent: US2005/70712,  2005,  A1. Location in patent: Page/Page column 42
[3] Patent: US2005/171131,  2005,  A1. Location in patent: Page/Page column 41
[4] Patent: US9212138,  2015,  B2. Location in patent: Page/Page column 42
[5] ChemMedChem,  2017,  vol. 12,  # 3,  p. 257 - 270
[6] Gargantilla, M., López-Fernández, J., Camarasa, M.-J., Persoons, L., Daelemans, D., Priego, E.-M., Pérez-Pérez, M.-J. (2021). Inhibition of XPO-1 Mediated Nuclear Export through the Michael-Acceptor Character of Chalcones. Pharmaceuticals, 14(11), 1131. https://doi.org/10.3390/ph14111131
[7] Soai, K., Sato, I., Shibata, T., Komiya, S., Hayashi, M., Matsueda, Y., Imamura, H., Hayase, T., Morioka, H., Tabira, H., Yamamoto, J., Kowata, Y. (2003). Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunction with asymmetric autocatalysis. Tetrahedron Asymmetry, 14(2), 185-188. https://doi.org/10.1016/S0957-4166(02)00791-7