Dimethylamine → HCID 19045285, compound

Participants

Reaction Conditions

Reaction Steps

In a solution of 2′-hydroxyacetophenone (10 g, 73.53 mmol) in 12 N HCl (160 mL) at room temperature was mixed with paraformaldehyde (2.43 g, 80.88 mmol) and stirred at 40° C. for 8 hours. The reaction was diluted with water, extracted with CH2Cl2 (3×100 mL), and concentrated using a rotary evaporator to provide 13 g of 5′-chloromethyl-2′-hydroxyacetophenone (98%). To a solution of 5′-chloromethyl-2′-hydroxyacetophenone (4 g, 21.74 mmol) in THF (50 mL) at room temperature was added dimethylamine in THF (13 mL, 26 mmol). The reaction mixture was stirred at 60° C. for 6 hours. It was quenched with water and neutralized with potassium carbonate to pH=8. Extract with CH2Cl2 (3×100 mL) followed by concentration using a rotary evaporator provided 3.86 g of 5′-(N,N-dimethylaminomethy)-2′-hydroxyacetophenone (92%). A solution of 5′-(N,N-dimethylaminomethy)-2′-hydroxyacetophenone (1.4 g, 7.25 mmol) and ethyl isonicotinate (1.1 g, 7.25 mmol) in THF (100 mL) at room temperature was mixed with NaH (1.02 g, 25.375 mmol) and was stirred at reflux for 6 hours. The reaction was quenched with water and extracted with CH2Cl2 (3×100 mL). The volume was reduced using a rotary evaporator to minimal and triturated with hexanes. The solid was collected by filtration to afford 1.85 g of the corresponding diketone (86%). A solution of the above diketone (1.85 g, 26.19 mmol) in HOAc (100 mL) was stirred at reflux for 2 hours. All the solvent was removed using a rotary evaporator to afford a solid residue. It was then re-dissolved in CH2Cl2, diluted with water and neutralized with potassium carbonate to pH=8, extracted with CH2Cl2 (3×100 mL) and concentrated using a rotary evaporator The solid residue was purified by column (SiO2, hexanes/EtOAc/MeOH=2:2:1) to afford 1.4 g of the intermediate (80%). A solution of the above intermediate (0.7 g, 2.34 mmol) in CH2Cl2 (20 mL) was mixed with HCl in ether (10 mL, 20 mmol) and stirred at room temperature for 30 min. The solid was collected by filtration and washed with CH2Cl2 and MeOH sequentially to obtain 0.48 g of the 6-((dimethylamino)methyl)-2-(pyridin-4-yl)-4H-chromen-4-one hydrochloride (60%) as an off-white solid.

Provenance & Evidence