Diethyl Ether → 2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)-7-chlorothieno[3,2-b]pyridine

To a solution of chlorothienopyridine 6 (22.93 g, 135 mmol) in THF (325 mL) at −5° C./−10° C. in a 1 L round-bottom flask was added n-BuLi (2.5 M in hexanes, 54.1 mL, 135 mmol) over 20 min. After 30 min, a solution of zinc chloride in ether (1M, 135 mL, 135 mmol) was added at −5° C./−10° C. over 20 min and the reaction mixture was allowed to warm-up to r.t. After 1 h, the bromide 28 (27.5 g, 113 mmol) and Pd(PPh3)4 (1.953 g, 1.169 mmol) in THF (48.8 mL) were added and the mixture was heated to reflux for 2 h, cooled down to r.t. and concentrated. The residue was diluted with DCM (1000 mL)/H2O (800 mL)/NH4OH (200 mL), stirred at r.t. for 1 h and the phases were separated. The aqueous phase was extracted with DCM (2×100 mL), the organic phase and the extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated. The residue was triturated with MTBE (100 mL) and collected by filtration (washed with MTBE, 2×20 mL) to give 29 (23.73 g, 71.3 mmol, 63.3% yield) as a beige solid. MS (m/z): 333.1 (M+1)

1. waitAfter 1 h
2. temperaturethe mixture was heated
3. temperatureto reflux for 2 h
4. temperaturecooled down to r.t.
5. concentrationconcentrated
6. additionThe residue was diluted with DCM (1000 mL)/H2O (800 mL)/NH4OH (200 mL)
7. customthe phases were separated
8. extractionThe aqueous phase was extracted with DCM (2×100 mL)
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was triturated with MTBE (100 mL)
13. filtrationcollected by filtration (washed with MTBE, 2×20 mL)

ORD record

ord-04514e00e309403f8c3a3cd69c8aca1e

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907091B2