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

To a solution of 7-chlorothieno[3,2-b]pyridine (1) (13.33 g, 79 mmol) in THF (204 mL) at −5° C./−10° C. was added n-BuLi (2.5 M in hexanes, 31.6 mL, 79 mmol) over 50 min. After 30 min, a solution of zinc chloride in ether (1M, 79 mL, 79 mmol) was added at −5° C./−10° C. over 50 min and the reaction mixture was allowed to warm-up to r.t. After 45 min, 2-bromo-5-(1,3-dioxan-2-yl)pyridine (316) (15.98 g, 65.5 mmol) and palladium tetrakistriphenylphosphine (2.27 g, 1.964 mmol) in THF (28 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 (600 mL), H2O (500 mL) and NH4OH (100 mL), stirred at r.t. for 1 h and the phases were separated. The aqueous phase was extracted with DCM (2×100 mL); the combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated. The residue was triturated with MTBE (150 mL), to afford intermediate 317 (12.796 g, 59% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.66-8.65 (m, 2H), 8.43 (d, J=0.8 Hz, 1H), 8.30 (d, J=8.4 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.59 (dd, J=5.0, 0.6 Hz, 1H), 5.68 (s, 1H), 4.19 (dd, J=11.6, 4.8 Hz, 2H), 3.99 (t, J=11.4 Hz, 2H), 2.07-2.01 (m, 1H), 1.49 (d, J=13.2 Hz, 1H). MS (m/z): 333.1 (M+H).

1. waitAfter 45 min
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 (600 mL), H2O (500 mL) and NH4OH (100 mL)
7. customthe phases were separated
8. extractionThe aqueous phase was extracted with DCM (2×100 mL)
9. dry with materialthe combined organic phases were dried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was triturated with MTBE (150 mL)

ORD-Eintrag

ord-c569d555171341bc9f5118e5b98086ca

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08759522B2