反应详情

To a mixture of 4,5-dihydro-5-[(pyrrolidino)carbonyl]imidazo[1,5-a]quinoxaline-3-carboxylic acid (I, EXAMPLE 322, 1.03 g) and 25 ml of dichloromethane cooled at 0° in an ice bath are added 1.15 ml of Methylamine and 0.650 ml) of ethyl cyanophosphonate, followed immediately by 0.811 g of 2-bromoethylamine hydrobromide. The ice bath is then removed and the reaction is stirred for 40 min. Aqueous sodium bicarbonate is then added. The mixture is stirred for 10 min and then partitioned with dichloromethane. The organic layers are dried over sodium sulfate and concentrated. The resulting mixture is stirred in 20 ml of THF and 3.3 ml of 1M potassium tert-butoxide is added dropwise over 2-3 min and the reaction is stirred an additional 10 min, at which time the reaction mixture is partitioned between ethyl acetate, water, and saline. The organic layers are dried over magnesium sulfate and concentrated. The crude product is chromatographed on silica gel (300 ml) eluting with methanol/methylene chloride (4/96), the appropriate fractions are pooled and concentrated to give the title compound, mp 217°-220°; MS (m/z) at 337; IR (mineral oil) 1651, 1512, 1416, 1357, 1396 cm-1 ; NMR (CDCl3) 1.81, 3.27, 4.05, 4.42, 4.99, 7.11-7.18, 7.26, 7.51, 8.03 δ.

1. temperaturecooled at 0° in an ice bath
2. customThe ice bath is then removed
3. additionAqueous sodium bicarbonate is then added
4. stirringThe mixture is stirred for 10 min
5. custompartitioned with dichloromethane
6. dry with materialThe organic layers are dried over sodium sulfate
7. concentrationconcentrated
8. stirringThe resulting mixture is stirred in 20 ml of THF
9. addition3.3 ml of 1M potassium tert-butoxide is added dropwise over 2-3 min
10. stirringthe reaction is stirred an additional 10 min, at which time the reaction mixture
11. customis partitioned between ethyl acetate, water, and saline
12. dry with materialThe organic layers are dried over magnesium sulfate
13. concentrationconcentrated
14. customThe crude product is chromatographed on silica gel (300 ml)
15. washeluting with methanol/methylene chloride (4/96)
16. concentrationconcentrated