2,4-Dimethoxyaniline → 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

Compound 8 (194 mg, 1 mmol) and 2,4-dimethoxyaniline (9e, 153 mg, 1 mmol) were taken in ethylene glycol and heated at 140° C. for 6 h. Then the reaction mixture was cooled and extracted with ethyl acetate from the aqueous layer and concentrated in vacuum. The compound was further purified by column chromatography using 60-120 silica gel to obtain 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10g as pure product. To a solution of 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (10 g, 150 mg, 0.48 mmol) and 1-(azidomethyl)-3,5-dimethoxybenzene (12d, 102 mg, 0.53 mmol) in 2:1 mixture of water and tert-butyl alcohol, sodium ascorbate (0.06 mmol) and copper (II) sulphate (0.005 mmol) were added sequentially. The reaction was stirred at room temperature for 12 h, TLC analysis indicated completion of reaction. The reaction mixture was concentrated under vacuum and extracted with EtOAc to give crude product. The crude was purified by column chromatography to afford pure product 6e (175 mg, 72%); mp: 147-149° C.; 1H NMR (500 MHz, CDCl3) δ 10.36 (s, 1H), 8.25 (dd, J=5.0, 3.0 Hz, 1H), 7.73 (dd, J=7.0 Hz, 1H), 7.53 (s, 1H), 7.15 (brs, 1H), 6.58-6.54 (m, 1H), 6.47-6.43 (m, 2H), 6.36 (s, 3H), 5.41 (s, 2H), 4.66 (d, J=5.2 Hz, 2H), 3.91 (s, 3H), 3.80 (s, 3H), 3.74 ppm (s, 6H) MS (ESI m/z): 505 [M+H]+. Yield: 72%

Provenance & Evidence