2-(3-methyl-1-oxo-3,4-dihydroisochromen-6-yl)acetaldehyde

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

Procedure: A 1:1 solution of dioxane:3N HCl was added to a flask containing of 99 mg (0.49 mmol) of 6-(1,3-dioxolan-2-ylmethyl)-3-methyl-3,4-dihydro-1H-isochromen-1-one; the reaction was then stirred at room temp overnight. The crude reaction mixture was then partitioned between water and DCM. The organic layer was washed with saturated sodium bicarbonate solution, followed by brine. The organic layer was then dried with magnesium sulfate, filtered and concentrated. The crude reaction mixture was then partitioned between water and DCM The organic layer was washed with saturated sodium bicarbonate solution The organic layer was then dried with magnesium sulfate filtered concentrated

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

Procedure: Freshly prepared (3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)acetaldehyde was dissolved in DCM. To the solution was added 2-methyl piperazine (221 mg, 2.2 mmol) followed by sodium cyanoborohydride (165 mg, 2.64 mmol). The reaction mixture was allowed to stir overnight before being quenched with 10 mL of 1N HCl followed by stirring for 30 minutes. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and extracted with DCM (3×50 mL). The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered, concentrated and purified via MPLC (30-100% (10% IPA in DCM/DCM) to afford 3-methyl-6-[2-(3-methylpiperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one. LC-MS (IE, m/z): 289 [M+1]+. before being quenched with 10 mL of 1N HCl by stirring for 30 minutes The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution extracted with DCM (3×50 mL) The combined organic layers were washed with water and brine dried with magnesium sulfate filtered concentrated purified via MPLC (30-100% (10% IPA in DCM/DCM)

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

Procedure: Freshly prepared (3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)acetaldehyde was dissolved in DCM. To the solution was added Boc-piperazine (671 mg, 3.6 mmol) followed by sodium triacetoxyborohydride (1.91 g, 9.0 mmol), the reaction mixture was allowed to stir overnight before being quenched with 10 mL of MeOH. The excess solvent was removed and the residue was re-redissolved in DCM; washed with water and brine, dried with magnesium sulfate, filtered, concentrated and purified via MPLC (50-100% EtOAc/Hex) to afford tert-butyl 4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazine-1-carboxylate. before being quenched with 10 mL of MeOH The excess solvent was removed the residue was re-redissolved in DCM washed with water and brine dried with magnesium sulfate filtered concentrated purified via MPLC (50-100% EtOAc/Hex)