The general procedure for the synthesis of 3-chloro-6-iodopyridazine from 3,6-dichloropyridazine was as follows: the intermediate (E)-3-{3-[3'-(1-adamantyl)-4'-hydroxyphenyl]-6-pyridazinyl}-2-propenoic acid ethyl ester was prepared as follows. a) Synthesis of 3-chloro-6-iodopyridazine. Followed the method reported in the literature (Goodman, A.J. et al., Tetrahedron, 1999, 55, 15067-15070). A suspension of 3,6-dichloropyridazine (5.000 g, 33.56 mmol), NaI (6.75 g, 45.0 mmol), and HI (55% to 58%, 25 mL) was stirred for 23 h at 44 °C (oil bath) under argon protection. After completion of the reaction, the mixture was cooled to room temperature and quenched with concentrated HCl. Subsequently, the pH was adjusted to 12 with NaOH, stirred for 10 min and extracted with CH2Cl2. The organic phase was washed with water and dried. The solvent was removed under reduced pressure to give 7.96 g (98% yield) of 3-chloro-6-iodopyridazine as a light yellow solid with a melting point of 114-116 °C (literature value: 110-112 °C). 1H NMR (CDCl3) δ 7.23 (d, J = 8.7 Hz, 1H, 4-ArH), 7.84 ppm (d, J = 8.7 Hz, 1H, 5-ArH).
