Hydrochloric Acid → Edicotinib Hydrochloride

Participants

Reaction Steps

A solution of 4-cyano-1H-imidazole-2-carboxylic acid[2-(4,4-dimethyl-cyclohex-1-enyl)-6-(2,2,6,6-tetramethyl-tetrahydro-pyran-4-yl)-pyridin-3-yl]-amide (49.2 mg, 0.107 mmol, as prepared in Example 15, step (h)) in EtOH (2 mL) was treated with HCl (26.6 μL, 0. 107 mmol, 4 M in dioxane) at room temperature for 1.5 h. The solvents were evaporated in vacuo, and the residue was dried under high vacuum overnight. The solid was dissolved in a minimum amount of EtOH (900 μL) with sonication and heating. While warm, the solution was slowly treated with hexanes (3 mL) to the cloud point. The mixture was heated again until clear, the sides of the vial were scratched, and the mixture was allowed to cool. The solid was filtered and air-dried to afford the title compound (20mg, 38%) as white crystals. 1H-NMR (CD3OD; 400 MHz): δ 9.17 (d, 1H, J=8.4 Hz), 8.10 (s, 1H), 7.95 (d, 1H, J=8.4 Hz), 6.38-6.32 (m, 1H), 3.76-3.65 (m, 1H), 2.54-2.46 (m, 2H), 2.25-2.19 (m, 2H), 1.98-1.91 (m, 2H), 1.76-1.65 (m, 4H), 1.43 (s, 6H), 1.30 (s, 6H), 1.15 (s, 6H). Mass spectrum (APCI, m/z): Calcd. for C27H35N5O2, 462.3 (M+H), found 462.3.

Provenance & Evidence