Acetic Acid → (6-Chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-acetic acid methyl ester

Participants

Reaction Steps

Dimethylamine (5.6 M solution in EtOH, 1.0 ml, 5.6 mmol, 1.5 equiv) was added to a solution of (6-chloro-3-formyl-quinoxalin-5-yl)-acetic acid methyl ester (966 mg, 3.65 mmol) in anhydrous THF (23 ml). The reaction mixture was stirred at room temperature for 18 hours. A solution of NaCNBH3 (275 mg, 4.37 mmol, 1.2 equiv) in methanol (6 ml) was added, immediately followed by the addition of acetic acid (1.10 g, 18.25 mmol, 5.0 equiv). After 5 minutes at room temperature, TLC analysis indicated complete conversion. The reaction mixture was diluted with water, adjusted to pH=8 with concentrated aqueous NaHCO3 solution, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of CH2Cl2/MeOH 99:1 to 90:10) to afford the title compound (303 mg, 28%) as a colorless solid and the regioisomeric (6-chloro-2-dimethylaminomethyl-quinoxalin-5-yl)-acetic acid methyl ester (48 mg, 5%). Data for (6-chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-acetic acid methyl ester: 1H NMR (400 MHz, CDCl3): δ=9.13 (s, 1H), 8.02 (d, J=9.0 Hz, 1H). 7.81 (d, J=9.0 Hz, 1H), 4.52 (s, 2H), 4.39 (s, 2H), 3.68 (s, 3H), 2.80 (s, 6H). MS (ES+): 294.2 (M+H)+. Data for (6-chloro-2-dimethylaminomethyl-quinoxalin-5-yl)-acetic acid methyl ester: 1H NMR (400 MHz, CDCl3): δ=9.30 (s, 1H), 7.98 (d, J=9.0 Hz, 1H), 7.84 (d, J=9.0 Hz, 1H), 4.49 (s, 2H), 3.82 (s, 2H), 3.71 (s, 3H), 2.34 (s, 6H). MS (ES+): 294.2 (M+H)+.

Provenance & Evidence