Diisopropylethylamine → 3-Fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)aniline

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, 200 mg, 0.477 mmol), 1-methyl-4-(prop-2-ynyl)piperazine (Example 17, Step A, 205.8 mg, 1.19 mmol), tetrakis(triphenylphosphine)palladium (0) (55.1 mg, 0.0477 mmol), copper(I) iodide (9.074 mg, 0.0477 mmol), N-ethyl-N-isopropylpropan-2-amine (2.49 ml, 14.3 mmol) and THF (25 mL). The reaction mixture was stirred at 60° C. until the starting material had been consumed (4 hours). Then the reaction mixture 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 100/1 to 10/1, v/v) to afford product (0.159 g, 84.2%). LRMS (APCI pos): m/e 397 (M+1). 1H NMR (400 MHz, CDCl3) δ 8.44 (d, 1H), 7.58 (s, 1H), 7.01 (t, 1H), 6.43-6.58 (m, 3H), 3.90 (br s, 2H), 3.61 (s, 2H), 2.48-2.83 (m, 8H), 2.38 (s, 3H).

Provenance & Evidence