Uses
Methyl 2,4-dichloropyrimidine-6-carboxylate serves as a precursor for synthesizing 6-amino-pyrimidine-4-carboxamides through amination, hydrogenation, hydrolysis, and amide coupling[2].
Synthesis
To a stirred suspension of orotic acid (20.00 g, 128.140 mmol) in POCI3(75 ml) was added DMF (catalytic amount, -0.5 ml) at ambient temperature, and the resulting reaction mixture was refluxed for 3 h. Excess of POC was removed by vacuum distillation after 3h of reflux. The obtained slurry was poured slowly into a 5 per cent mixture of methanol in chloroform (200 ml) at 0°C and stirred for 30 min. The organic layer obtained was washed with a saturated solution of NaHCC>3 (3 x 200 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure, yielding Methyl 2,4-dichloropyrimidine-6-carboxylate (19.00 g, 91 .800 mmol).
References
[1] Patent: WO2018/167276, 2018, A1. Location in patent: Paragraph 00131; 00132; 00133
[2] Wilson, C. R., Gessner, R. K., Moosa, A., Seldon, R., Warner, D. F., Mizrahi, V., de Melo, C. S., Simelane, S. B., Nchinda, A., Abay, E., Taylor, D., Njoroge, M., Brunschwig, C., Lawrence, N., Boshoff, H. I. M., III, C. E. B., and Frederick A. Sirgel, van Helden, P., Harris, C. J., … Chibale, K. (2017). Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies. Journal of Medicinal Chemistry, 60 24, 10118–10134.
https://doi.org/10.1021/acs.jmedchem.7b01347
