Potassium Iodide → HCID 86723820, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-chloro-6-isopropoxy-2,3-dihydro-isoindol-1-one (133a, 120 mg, 0.532 mmol), 2-benzyloxy-3-chloromethyl-4,6-dimethyl-pyridine (Cpd Z, 139 mg, 0.532 mmol), cesium carbonate (260 mg, 0.798 mmol), and potassium iodide (132 mg, 0.798 mmol) in DMF (6 mL) was stirred at 100° C. overnight. The solution was cooled to room temperature and the reaction mixture partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was separated, washed with water (50 mL) and brine (50 mL), dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography (silica gel, heptanes/EtOAc) and the residue concentrated under vacuum. The residue was treated with TFA at room temperature overnight. Excess TFA was removed under vacuum and the resulting residue was partitioned between ethyl acetate (50 mL) and sodium bicarbonate (50 mL). The organic phase was separated, washed with brine (50 mL), dried over sodium sulfate, and concentrated under vacuum. The residue was purified by column chromatography (silica gel, MeOH/EtOAc, 1/10) to give the title compound (Example 133, 20 mg, 12% yield over two steps) as a solid. 1H NMR (400 MHz, chloroform-d) δ 12.09 (br. s., 1H), 7.08-7.13 (m, 1H), 7.02-7.07 (m, 1H), 5.94 (s, 1H), 4.66 (s, 2H), 4.44-4.55 (m, 1H), 4.31 (s, 2H), 2.37 (s, 3H), 2.24 (s, 3H), 1.36 (d, J=6.06 Hz, 6H): MS 361 [M+H].

Provenance & Evidence