Phosphorus oxychloride → HCID 67453355, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(3-chlorophenyl)-4,5-dihydro-1,2,4-triazin-6(1H)-one (6.0 g, 29 mmol) dissolved in dioxane (75 mL) was added MnO2 (10 g, 120 mmol). The mixture was stirred at 90° C. for 18 h. After filtering through diatomaceous earth and rinsing with hot dioxane, the combined organics were evaporated to dryness in vacuo. The crude residue (⅓ was used) was dissolved in POCl3 (10 mL, 108 mmol) and heated to 70° C. for 2.5 h. The mixture was allowed to cool to rt and evaporated to dryness in vacuo. The residue was dissolved in EtOAc/ether (1:1) and washed with 1 M NaOH. The organic phase was evaporated to dryness and dissolved in NMP (5.0 mL) in a microwave vial. Potassium carbonate (1.0 g) was added followed by (2-(4-fluorophenyl)-2-methylpropan-1-amine (2.0 g, 12 mmol), and the mixture was heated in a microwave reactor to 165° C. for 20 min. The solution was diluted with EtOAc and washed with saturated NaCl (4×), dried over Na2SO4, and evaporated to dryness. Purification using silica gel chromatography (0-35% EtOAc/hexanes) gave the desired product (430 mg) as an orange film.

Provenance & Evidence