Diphenyl Ether → 4-Amino-2-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-6(7H)-one

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Reaction Steps

To a stirred suspension of methyl 4-amino-2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (Description 35) (1.617 g, 4.70 mmol) in ethanol (20 mL) was added aqueous NaOH (5M) (4.70 mL, 23.48 mmol). The suspension was then refluxed under nitrogen for ca. 2 h. The reaction mixture was then cooled to RT and concentrated in vacuo. The residue was partitioned between DCM and water (ca. 50 mL each) and acidified to ca. pH 7 using aqueous HCl (5M). The aqueous layer was separated and re-extracted with DCM (ca. 50 mL×2) and the combined organic layer passed through a phase separator and concentrated in vacuo. The residue was dissolved in diphenyl ether (20 mL, 126 mmol) and heated to 200° C. under nitrogen atmosphere for ca. 2 h. The mixture was then cooled to RT, passed through SCX cartridge (eluting with MeOH followed by 2M NH3 MeOH) and the basic fractions combined and concentrated in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-20% MeOH in DCM, to afford the title compound (588 mg). LCMS (A) m/z: 285 [M−1]−, Rt 1.10 min (acidic).

Provenance & Evidence