Potassium phthalamide → 2-((5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of (5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl methanesulfonate (816 mg, 2.25 mmol, intermediate 74) in dry DMSO (10 mL) was added potassium phthalamide (2.1 g, 11.3 mmol) in a single portion. The reaction mixture was heated at 180° C. for 5 hr, cooled to room temperature and diluted with EtOAc (50 mL) and water (30 mL). The organic layer was washed with water (3×30 mL), 2 N NaOH (2×20 mL) and water (20 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-((5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione as a colourless solid (317 mg, 35%). 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.93-7.88 (m, 2H), 7.82-7.76 (m, 2H), 6.31 (s, 1H), 4.14 (s, 3H), 4.06 (d, J=11.8 Hz, 2H), 3.85 (d, J=11.8 Hz, 2H), 3.51 (s, 2H), 1.92 (q, J=7.6 Hz, 2H), 1.14 (t, J=7.6 Hz, 3H).

Provenance & Evidence