Potassium Carbonate → (4-(6-Amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl ester

Participants

Reaction Steps

Into a microwave vial was placed [4-(6-amino-5-chloro-pyrimidin-4-ylamino)-phenyl]-acetic acid ethyl ester (1.4 g; 3.423 mmol; 1.0 eq.), (4-phenoxyphenyl)boronic acid (1598.9 mg; 7.470 mmol; 2.18 eq.), palladium acetate (38.4 mg; 0.171 mmol; 0.1 eq.), dicyclohexyl-(2′,6′-dimethoxy-biphenyl-2-yl)-phosphane (140.5 mg; 0.342 mmol; 0.1 eq.), potassium carbonate (1419.2 mg; 10.269 mmol; 3.0 eq.) suspended in dioxane (15.0 ml) and water (1.5 ml). The vial was flushed with nitrogen. The reaction vial was run in a microwave for 3 hours at 150° C. The mixture was filtered, quenched in water and extracted with EtOAc (3×). The combined organic layer were dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified using Biotage column chromatography (50/50% Hexanes/EtOAc to 100% EtOAc). Fractions containing the desired product were collected and concentrated to afford (4-(6-amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl ester (1.43 g, 90% yield) as a yellow foam. MS: m/z=441 [M+H]+. 1H-NMR (DMSO-d6) δ 8.06 (s, 1H), 7.45 (t, 4H), 7.34 (d, 2H), 7.16 (dd, 8H), 5.77 (bs, 2H), 4.10 (q, 2H), 3.56 (s, 2H), 1.20 (t, 3H).

Provenance & Evidence