反应详情

Dissolve 1-(4-imidazo[1,2-a]pyridin-7-yl-pyridin-2-yl)-propan-2-one (3.9 g, 15.5 mmol) in methanol (400 mL) under nitrogen. Add morpholine hydrochloride (38.4 g, 20 equiv.) followed by 3 {acute over (Å)} Sieves (7.8 g, powdered and dried in a vacuum oven at 100° C. overnight). Stir five minutes then add sodium cyanoborohydride (1.0 M in THF, 28 mL, 1.8 equiv.) via syringe and stir at room temperature for 5 days. Filter to remove insoluble material, washing with methanol. Concentrate to dryness then make basic with 20% NaOH (aq) and extract with ethyl acetate. Wash organics with aqueous saturated sodium chloride then dry over MgSO4. Filter and concentrate then purify by silica gel (Ethyl Acetate→5% Methanol:DCM→10% Methanol:DCM→5% 2M NH3 in methanol:DCM→10% 2 M NH3 in Methanol:DCM) to give product as a tan solid (3.7 g, 74%). MS (ES), m/z 323 (M+1).

1. customdried in a vacuum oven at 100° C. overnight)
2. filtrationFilter
3. customto remove insoluble material
4. washwashing with methanol
5. concentrationConcentrate to dryness
6. extractionextract with ethyl acetate
7. dry with materialWash organics with aqueous saturated sodium chloride then dry over MgSO4
8. filtrationFilter
9. concentrationconcentrate
10. customthen purify by silica gel (Ethyl Acetate→5% Methanol:DCM→10% Methanol:DCM→5% 2M NH3 in methanol:DCM→10% 2 M NH3 in Methanol:DCM)