Diethyl Malonate → 2-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-benzo[4,5]thieno[2,3-d]pyrimidin-7-yl}-malonic acid diethyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirring suspension of (7-bromo-benzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-amine (150 mg, 0.291 mmol) in malonic acid diethyl ester (2 mL, 2 g, 12.5 mmol) was added sodium hydride (60%, 35.0 mg, 0.874 mmol). The resulting mixture was bubbled with N2 for 2 min, followed by addition of biphenyl-4-yl-di-tert-butyl-phosphane (4.35 mg, 0.015 mmol), and tris(dibenzylideneacetone)dipalladium (13.3 mg, 0.015 mmol). The mixture was bubbled with N2 for an additional 2 min. The reaction mixture was stirred at 135-140° C. for 20 min. It was cooled to rt, and concentrated in vacuo. The residue was purified by chromatography (hexane/EtOAc=2/1 to 1/1) to give the product (130 mg, 75%). 1H-NMR (CDCl3-d) δ 8.56 (s, 1H), 8.05 (d, 1H), 8.00 (s, 1H), 7.82 (b, 1H), 7.74 (s, 1H), 7.66 (d, 1H), 7.49 (q, 1H), 7.34-7.39 (m, 1H), 7.20-7.26 (m, 2H), 6.99-7.05 (m, 2H), 5.18 (s, 2H), 4.80 (s, 1H), 4.20-4.31 (m, 4H), 1.28-1.34 (m, 6H); LCMS RT=4.23 min, [M+H]+=594.1.

Provenance & Evidence