1-sulfanylidene-4H-isoquinolin-3-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 mL round bottom flask was added 1-thioxo-1,4-dihydro-2H-isoquinolin-3-one (250 mg, 1.41 mmol), and 2-phenylpropan-2-thiol (192 mg, 1.41) followed by a solution of TFA (10 mL, 20% v/v in DCM). The reaction mixture was stirred under Ar for 1 h, neutralized with NaHCO3 (100 mL, sat. aq.), and then extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, and then the solvent was removed by rotary evaporation to yield a crude residue. The crude residue was purified via silica gel chromatography to provide the title compound as an orange solid (188 mg, 0.636 mmol, 45%). 1H NMR (400 MHz, CDCl3): δ ppm 8.11 (d, J=8.79 Hz, 1H), 7.55 (t, J=7.47 Hz, 3H), 7.42-7.50 (m, 1H), 7.14-7.29 (m, 5H), 6.74 (s, 1H), 1.95 (s, 6H). LC/MS m/z 296 [M+H]. extracted with EtOAc The organic phase was washed with brine dried over Na2SO4 the solvent was removed by rotary evaporation to yield a crude residue The crude residue was purified via silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 mL round bottom flask was added 1-thioxo-1,4-dihydro-2H-isoquinolin-3-one (0.8 g, 4.51 mmol), K2CO3 (1.9 g, 13.5 mmol), and absolute EtOH (15 mL) followed by 1-(bromomethyl)-2-chlorobenzene (0.88 g, 4.29 mmol). Upon completion of addition, the reaction mixture was stirred for 18 h. At the conclusion of this period, the reaction mixture was acidified with a solution of citric acid (100 mL, 10% w/v), extracted with EtOAc (100 mL), washed with brine (75 mL) and then dried over Na2SO4. The solvent was removed under vacuum to yield a residue. The residue was purified via silica gel chromatography (20% EtOAc:Hex) to yield the title compound as a pale yellow solid (1.1 g, 3.64 mmol, 81%). 1H NMR (400 MHz, DMSO-d6): δ ppm 8.05 (d, J=8.35 Hz, 1H), 7.59-7.64 (m, 1H), 7.50-7.57 (m, 2H), 7.37-7.42 (m, 1H), 7.31 (ddd, J=8.46, 6.92, 1.32 Hz, 1H), 7.16-7.23 (m, 2H), 6.71 (s, 1H), 5.92 (br. s., 1H), 4.67 (s, 2H). LC/MS m/z 302 [M+H]. Upon completion of addition extracted with EtOAc (100 mL) washed with brine (75 mL) dried over Na2SO4 The solvent was removed under vacuum to yield a residue The residue was purified via silica gel chromatography (20% EtOAc:Hex)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round bottom flask was added anhydrous aluminum chloride powder (21.6 g, 162.2 mmol) and 1,1,2,2-tetrachloroethane (20 mL). The resulting solution was cooled to 0° C. under Ar and then a solution of phenylacetyl isothiocyanate (12.5 g, 70.5 mmol) in 1,1,2,2-tetrachloroethane (10 mL) was added dropwise via addition funnel over a period of 10 min. Upon completion of addition, the reaction mixture was stirred at 95° C. for 1 h during which time the slurry became a dark brown solution. The reaction mixture was then allowed to cool to RT. Once at the prescribed temperature, the reaction mixture was carefully quenched with a solution of cold HCl (250 mL, 2.4 N). The resultant beige precipitate was collected by vacuum filtration, air dried for 0.5 h and then recrystallized from glacial AcOH and decolorizing charcoal to yield the title compound as an orange crystalline solid (7.2 g, 40.6 mmol, 58%). 1H NMR (400 MHz, CDCl3): δ ppm 3.29 (s, 1H), 11.78 (s, 1H), 8.57 (d, 1H, J=8.35 Hz), 7.59-LC/MS m/z [M+H]. Upon completion of addition to cool to RT Once at the prescribed temperature, the reaction mixture was carefully quenched with a solution of cold HCl (250 mL, 2.4 N) The resultant beige precipitate was collected by vacuum filtration, air dried for 0.5 h recrystallized from glacial AcOH