Sodium Carbonate → 6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine

Temperature

60 °C

Alternatively, to a mixture of 4-bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine (D7) (1 g, 2.97 mmol), 4-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.857 g, 3.12 mmol) in DME (18 mL) and MeOH (2.0 mL) was added bis(triphenylphosphine)palladium(II) chloride (0.208 g, 0.297 mmol) and 2M sodium carbonate aq. solution (14.84 mL, 29.7 mmol). The mixture was stirred at 60° C. for 1 hour. The mixture was cooled to RT and filtered. The solid was washed with excess ethyl acetate and the filtrate concentrated in vacuo. The residue aqueous was extracted with ethyl acetate (4×200 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated. The residue was purified on normal phase chromatography eluting with a gradient of 0-30% ethyl acetate in cyclohexane to give the title compound (344 mg). LCMS (A): m/z (M+H)+ 358/360, C17H16BrN3O requires 357/359 (acidic).

1. temperatureThe mixture was cooled to RT
2. filtrationfiltered
3. washThe solid was washed with excess ethyl acetate
4. concentrationthe filtrate concentrated in vacuo
5. extractionThe residue aqueous was extracted with ethyl acetate (4×200 mL)
6. dry with materialThe combined organics were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified on normal phase chromatography
10. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane

ORD record

ord-6d4cd7e6f00c4e97a19a3fb5825dd1fd

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08877742B2