Uses
Ethyl 4,6-Dichloronicotinate acts as a reactant in the preparation of (acylamino)aminonaphthyridinones as novobiocin analogs and Hsp90 inhibitors, their antitumor activities in human breast cancer cell lines, and the effects on aptoptosis and cell cycle advancement of selected compounds.
Uses
Ethyl 4,6-dichloronicotinate is an important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals, and dyestuffs. It is also used as a fine chemical intermediate. Ethyl-4,6-dichloronicotinate could be used as a starting material to synthesize 6-chlorothieno[3,2-c]pyridine-2-carbohydrazide-hydrazone subsidiaries[1].
Synthesis
The general procedure for the synthesis of ethyl 4,6-dichloronicotinate from ethyl 4,6-dihydroxynicotinate was as follows: ethyl 4,6-dihydroxynicotinate (60 g, 0.328 mol) was slowly added to phosphorus triclosan (POCl3, 500 mL), followed by heating and refluxing for 2 hours. Upon completion of the reaction, the excess phosphorous trichloride was removed by distillation under reduced pressure. The residue was carefully poured into ice water, stirred for 30 min, and then extracted with ethyl acetate (EtOAc, 3 times). The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4) and finally concentrated under vacuum to give ethyl 4,6-dichloronicotinate (65 g, 90% yield). The product was identified by 1H NMR (300 MHz, DMSO-d6): δ 8.80 (s, 1H), 7.95 (s, 1H), 4.34 (q, J=6.9 Hz, 2H), 1.31 (t, J=6.9 Hz, 3H); Mass Spectra (ESI) m/z: 220.1 [M+H]+.
References
[1] N. Rao, K. Prasad, M. Rao. “Synthesis and Antibacterial Evaluation of Hydrazone Derivatives Bearing 6-Chlorothieno[3,2-c]pyridine Moiety.” Asian Journal of Chemistry 1 1 (2019).
