Triethylamine → HCID 178500476, compound

Participants

Reaction Steps

A mixture of 0.016 g (0.093 mmol) of palladium chloride and 0.0486 g (0.185 mmol) of triphenylphosphine in 5 mL of acetonitrile is stirred under nitrogen at room temperature for 30 minutes. To this mixture is added an additional 10 mL of acetonitrile and 0.80 g (1.89 mmol) of dimethyl N-(2-fluoro-5-iodobenzoyl)L-glutamate, 0.50 g (1.85 mmol) of 2-pivaloylamino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine, 0.0088 g (0.046 mmol) of copper iodide, and 0.54 mL (3.89 mmol) of triethylamine. The mixture is then heated to reflux for 3 hours. After cooled to room temperature, the solvent is removed in vacuo and the residue is flash chromatographed on silica gel using 1:19 methanol:chloroform as the eluent to yield 0.92 g (88%) of dimethyl N-(2-fluoro-5-[2-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)-ethynyl]-benzoyl)-L-glutamate as a dark yellow solid m.p. 189°-191° C. (dec); Rf =0.48 (1:19 methanol:chloroform), Mass (FD)=565; IR (KBr, cm-1)=1146, 1228, 1263, 1440, 1488, 1549, 1596, 1607, 1622, 1673, 1742; UV (EtOH) λmax =319 (epsilon=30600), 259 (epsilon=11200), 212 (epsilon=42100); 1NMR (300 MHz, CDCl3) delta 1.38 (s, 9H), 2.19 (m, 1H), 2.3-2.6 (m, 3H), 3.72 (s, 3H), 3.85 (s, 3H), 4.95 (m, 1H), 7.21 (dd, 1H, J=8.5, 11.2 Hz), 7.45 (m, 1H), 7.68 (m, 1H), 8.26 (dd, 1H, J=2.0, 7.2 Hz), 8.37 (s, 1H), 8.63 (d, 1H, J=2.2 Hz), 9.0 (d, 1H, J=2.0 Hz).

Provenance & Evidence