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

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Reaction Steps

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)

Provenance & Evidence