Reaction Steps
5-[2-(3-Bromo-phenylamino)-pyrimidin-4-yl]-thiophene-2-carboxylic acid (1-phenyl-ethyl)-amide (20 mg, 41 μmol), 3-dimethylamino pyrrolidine (6 mg, 0.5 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (1.5 mg, 2 μmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (2 mg, 5 μmol) were suspended in 0.2 mL lithium bis(trimethylsilyl)amide solution in THF (1M). The reaction mixture was stirred at 65° C. for 48 hours. The reaction was quenched with 1 mL MeOH and concentrated and the crude product was redissolved in DMSO and purified by mass triggered reverse phase HPLC to afford 1.2 mg of pure 5-{2-[3-(3-Dimethylamino-pyrrolidin-1-yl)-phenylamino]-pyrimidin-4-yl}-thiophene-2-carboxylic acid (1-phenyl-ethyl)-amide (2.5 μmol, 6%, 1:1 mixture of diastereomers). 1H NMR (500 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.94 (d, J=8 Hz, 1H), 8.50 (d, J=5 Hz, 1H), 7.97 (d, J=4 Hz, 1H), 7.92 (d, J=4 Hz, 1H), 7.39 (d, J=5 Hz, 2H), 7.33 (m, 4H), 7.23 (t, J=7 Hz, 1H), 7.18 (s, 1H), 6.98 (m, 1H), 6.17 (d, J=7.5 Hz, 1H), 5.14 (quintet, J=6.5 Hz, 1H), 3.45 (q, J=8 Hz, 1H), 3.39 (t, J=8 Hz, 1H), 3.32 (m, 2H), 3.02 (q, J=8 Hz, 1H), 2.77 (m, 1H), 2.15 (s, 6H), 1.79 (m, 1H), 1.49 (d, J=6.5 Hz, 3H). MS: m/z 513 (M+H+).
