反应详情

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).

1. stirringvigorously stirred for 2 hours
2. customAfter the phases separated
3. filtrationa white solid was collected by filtration
4. additionmixed with water and dichloromethane
5. dissolutionit did not completely dissolve
6. filtrationFiltration
7. customprovided a second water/dichloromethane mixture, which
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with dichloromethane (3×100 mL)
10. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (250 mL)
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationThe filtrate was concentrated on a rotary evaporator at 45° C. until solid
14. customto form in the flask
15. stirringwith stirring
16. waitthe mixture was granulated for 1 hour
17. filtrationFiltration