1,4-Dioxane → 6-(Benzylthio)-1-(4-chloro-2-methoxyphenyl)isoquinoline

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with 6-(benzylthio)-1-chloroisoquinoline (from STEP 1 of INTERMEDIATE LLL) (688.23 mg, 2.408 mmol), (4-chloro-2-methoxyphenyl)boronic acid (494 mg, 2.65 mmol), Pd(AmPhos)2Cl2 (85 mg, 0.120 mmol), potassium phosphate (1534 mg, 7.22 mmol), dioxane (6020 μl), and water (2007 μl). The vial was flushed with Ar (g), then 1,4-dioxane (6020 μl) and water (2007 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 100° C. The mixture was cooled to room temperature, then diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (40-g, 10 to 40%, then 40-70% EtOAc/Heptane, 25-g silica gel loading column) to give 6-(benzylthio)-1-(4-chloro-2-methoxyphenyl)isoquinoline (704.36 mg, 1.797 mmol, 74.6% yield) as a light-yellow foam: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.56 (d, J=5.8 Hz, 1H), 7.65 (d, J=1.9 Hz, 1H), 7.55-7.48 (m, 2H), 7.44-7.39 (m, 2H), 7.38-7.27 (m, 5H), 7.11 (dd, J=1.9, 8.1 Hz, 1H), 7.04 (d, J=1.9 Hz, 1H), 4.30 (s, 2H), 3.70 (s, 3H); m/z (ESI) 392.2 (M+H)+.

Provenance & Evidence