反应详情

温度

80 °C

A vial was charged with 2,5-difluorophenylboronic acid (0.035 g, 0.222 mmol), PdCl2(dppf)-CH2Cl2 adduct (8.65 mg, 10.59 μmol), (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.100 g, 0.212 mmol), and potassium phosphate (0.450 g, 2.118 mmol). Dioxane (2 mL) and water (1 mL) were added, the vial was flushed with argon, sealed and heated to 80° C. 1 hour. The reaction mixture was cooled to rt and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (7.50 mg, 10.59 μmol) was added, followed by 2-fluoropyridin-4-ylboronic acid (0.045 g, 0.318 mmol). The reaction mixture was again capped under argon and was heated to 80° C. for and additional hour. The reaction mixture was then diluted with 2-MeTHF, dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (95:5 EtOAc/MeOH)/DCM] gave (S)-7-(2,5-difluorophenyl)-3-(2-fluoropyridin-4-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.028 g, 0.059 mmol, 27.9% yield) as a light yellow solid. [M+H]+=475.0

1. customthe vial was flushed with argon
2. customsealed
3. custom1 hour
4. temperatureThe reaction mixture was cooled to rt
5. customThe reaction mixture was again capped under argon
6. temperaturewas heated to 80° C. for and additional hour
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customPurification of the crude residue by column chromatography [0-100% (95:5 EtOAc/MeOH)/DCM]