Sodium Carbonate → 4-(2-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

Participants

Reaction Conditions

Reaction Steps

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 0.461 g, 1.19 mmol), 1,4-dioxaspiro[4.5]dec-7-en-8-ylboronic acid (0.659 g, 3.58 mmol), tetrakis(triphenylphosphine)palladium (0.276 g, 0.239 mmol), Na2CO3 (2.98 ml, 5.97 mmol) and dioxane (50 mL). The reaction mixture was stirred at 100° C. until the starting material had been consumed (overnight). Then the reaction was cooled to room temperature and partitioned between EtOAc (100 mL) and H2O (100 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×100 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (0.418 g, 87.9%). LRMS (APCI pos): >97% purity, 254 nm, m/e 399 (M+1). 1H NMR (400 MHz, CDCl3) δ 8.40 (d, 1H), 7.34 (s, 1H), 7.01 (t, 1H), 6.42-6.56 (m, 3H), 6.28 (s, 1H), 4.04 (s, 4H), 3.82 (br s, 2H), 2.80 (m, 2H), 2.52 (m, 2H), 1.98 (m, 2H).

Provenance & Evidence