反应详情

A mixture of (S)-tert-butyl 2-acetylmorpholine-4-carboxylate (2.29 g, 10.0 mmol), ammonium acetate (7.70 g, 100 mmol), sodium cyanoborohydride (0.94 g, 15.0 mmol), and 5 angstrom molecular sieves (10 g) in methanol (50 mL) was stirred at room temperature under nitrogen for 16 hours. The sieves were removed by filtration and the filtrate was concentrated. A solution of 1 N NaOH was added until the pH reached 12. The mixture was extracted with CH2Cl2 and the combined extracts were dried over MgSO4, filtered and concentrated. The resulting light yellow oil (2.17 g) was dissolved in THF (40 mL) and 5,7-dichloropyrido[3,4-b]pyrazine (2.00 g, 10.0 mmol) and DIPEA (1.94 g, 15.0 mmol) were added. The mixture was heated to reflux for 48 hours. The volatile components were evaporated and the residue was extracted with ethyl acetate. Ethyl acetate was washed with brine and dried. The solvent was removed in vacuo. The crude residue was purified by silica-gel chromatography eluting with Hexane-50% EtOAc/Hexane (gradient) then C18 column to afford the subtitled compound as brown oil 450 mg. MS (m/z): 394 (M+H)+

1. customThe sieves were removed by filtration
2. concentrationthe filtrate was concentrated
3. additionA solution of 1 N NaOH was added until the pH
4. extractionThe mixture was extracted with CH2Cl2
5. dry with materialthe combined extracts were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe resulting light yellow oil (2.17 g) was dissolved in THF (40 mL)
9. temperatureThe mixture was heated
10. temperatureto reflux for 48 hours
11. customThe volatile components were evaporated
12. extractionthe residue was extracted with ethyl acetate
13. washEthyl acetate was washed with brine
14. customdried
15. customThe solvent was removed in vacuo
16. customThe crude residue was purified by silica-gel chromatography
17. washeluting with Hexane-50% EtOAc/Hexane (gradient)