Synthesis
The general procedure for the synthesis of 2-oxo-1,2-dihydropyridine-3-carbonitrile from 2-chloro-3-cyanopyridine was as follows: acetic acid (826 mL) was slowly added to 2-chloro-3-cyanopyridine (250 g), and the mixture was subsequently heated to reflux and held for 48 hours. Upon completion of the reaction, the reaction mixture was quenched by careful pouring into an ice-water mixture. The resulting precipitate was collected by filtration, washed well with deionized water and dried under appropriate conditions to give the target product 2-hydroxy-3-cyanopyridine. The yield of this step was 95%. The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 12.57 (s, 1H), 8.16 (dd, J = 3.6 Hz, 1H), 7.80 (dd, J = 3.6 Hz, 1H), 6.37 (t, 1H); the mass spectrum (ES) showed m/z of 121.
References
[1] Tetrahedron Letters, 2004, vol. 45, # 35, p. 6633 - 6636
[2] Patent: WO2014/207508, 2014, A1. Location in patent: Page/Page column 55
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 18, p. 7624 - 7643
[4] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 21, p. 5738 - 5746
[5] Synthetic Communications, 2011, vol. 41, # 19, p. 2859 - 2869
