7-Chlorothieno[3,2-b]pyridine → 2-(6-(1,3-Dioxan-2-yl)pyridin-3-yl)-7-chlorothieno[3,2-b]pyridine

To a stirred solution of 7-chlorothieno[3,2-b]pyridine (12.08 g, 71.2 mmol) in THF (138 mL) at −15° C. was added n-BuLi (30.7 mL, 77.0 mmol). After 30 min, a solution of ZnCl2 0.5 M in THF (142 mL, 71.2 mmol) was added at −15° C. and the reaction mixture was allowed to warm to RT over 45 min. A solution of palladium tetrakistriphenylphosphine (1.266 g, 1.096 mmol) and bromide 278 (13.37 g, 54.8 mmol) in THF (18.5 mL) was added and the mixture was heated to reflux for 2 h then concentrated. The residue was diluted with water and ammonium hydroxide and extracted with DCM. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was triturated with MTBE to afford the title compound 279 (10.70 g, 32.2 mmol, 59% yield) as light brown solid. MS (m/z): 333.33 (M+H).

1. temperaturethe mixture was heated
2. temperatureto reflux for 2 h
3. concentrationthen concentrated
4. additionThe residue was diluted with water and ammonium hydroxide
5. extractionextracted with DCM
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was triturated with MTBE

ORD record

ord-d45fb2b9a1304b0fb4334e3338588d68

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08906852B2