反应详情

A solution of 2-((5-amino-3-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrile (5.58 g, 11.82 mmol) in 100 mL 2-MeTHF under nitrogen atmosphere was treated with trimethylaluminum [2N in heptane (7.98 mL, 15.96 mmol)]. After stirring for 10 minutes at RT, the reaction mixture was heated to 80° C. for 90 minutes. The reaction mixture was cooled to RT and quenched with MeOH. The reaction mixture was treated with saturated Rochelle's salt solution and vigorously stirred for an additional hour. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure. Purification of the crude residue by column chromatography [0-80% (90:10:1 DCM/MeOH/NH4OH)/DCM] gave 3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (Intermediate 2, 2.97 g).

1. temperaturethe reaction mixture was heated to 80° C. for 90 minutes
2. temperatureThe reaction mixture was cooled to RT
3. customquenched with MeOH
4. additionThe reaction mixture was treated with saturated Rochelle's salt solution
5. stirringvigorously stirred for an additional hour
6. customThe organic layer was separated
7. washwashed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated under reduced pressure
10. customPurification of the crude residue by column chromatography [0-80% (90:10:1 DCM/MeOH/NH4OH)/DCM]