Azetidine → 4-(Azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine

Participants

Reaction Steps

A solution of azetidine (9.21 g, 161 mmol) in dichloromethane (75 mL) was added to a solution of 4-chloro-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine (38.14 g, 153.4 mmol) in dichloromethane (310 mL). After stirring for 5 minutes, the reaction was treated with aqueous sodium bicarbonate solution (0.89 M, 260 mL, 231 mmol) and vigorously stirred for 2 hours. After the phases separated, a white solid was collected by filtration and mixed with water and dichloromethane; it did not completely dissolve. Filtration provided a second water/dichloromethane mixture, which was combined with the original filtrate. The layers were separated, and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (250 mL), then dried over sodium sulfate and filtered. The filtrate was concentrated on a rotary evaporator at 45° C. until solid began to form in the flask. tert-Butyl methyl ether (400 mL) was added with stirring, and the mixture was granulated for 1 hour. Filtration provided the product as a white solid. Yield: 36.07 g, 133.9 mmol, 87%. 1H NMR (400 MHz, CDCl3) δ 2.23-2.31 (m, 2H), 2.65 (s, 3H), 3.97 (s, 3H), 3.98-4.08 (m, 4H), 7.61 (s, 1H), 7.62 (s, 1H), 7.85 (s, 1H).

Provenance & Evidence