Potassium Hydroxide → 2-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-yl]-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide

Participants

Reaction Steps

A solution of 1,4-benzodioxan-6-ylbromomethyketone (0.051 g, 0.2 mmol), methyl 2-(aminocarbonothioyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (0.05 g, 0.2 mmol) in 1,4-dioxane (1 mL) heated at 40° C. for 2 h. Upon cooling to room temperature, the solvent was removed under reduced pressure to afford a solid residue. To the solid residue was added hydroxylamine hydrochloride (0.056 g, 0.8 mmol), potassium hydroxide (0.09 g, 1.6 mmol), and methanol (2 mL). The mixture was heated at 80° C. for 2 h. Upon cooling to room temperature, the solvent was then removed under reduced pressure, the residue dissolved in DMSO (1 mL) and purified on Gilson prep-HPLC [236 nm, rt=7.54 min (12 min), 30-70% gradient MeCN—H2O] to give 28.6 mg (35%) of the title compound as a white solid. LCMS: (FA) ES+ 410; 1H NMR (MeOD, 400 MHz) δ 8.51 (s, 1H), 7.60 (m, 2H), 7.33 (m, 3H), 6.82 (s, 2H), 4.74 (m, 2H), 4.25 (m, 4H), 3.84 (m, 2H), 3.08 (m, 2H).

Provenance & Evidence