Methyl phenylacetate → 7-Chloro-2-(methylsulfanyl)-6-phenylpyrido[2,3-d]pyrimidine

Participants

Reaction Steps

To the solution of methyl phenylacetate (0.945 g, 6.29 mmol) in THF (20 mL) at −78° C. was added LHMDS (1 M, 6.6 mL) and stirred for 1 h. 4-amino-2-(methylthio)pyrimidine-5-carbaldehyde (1-2; 0.507 g, 3.0 mmol) was added. The mixture was stirred and warmed to rt. The reaction was quenched with saturated NH4Cl solution and extracted with CH2Cl2. The combined organic layer was dried, filtered and concentrated. The residue was dissolved in CH3CN (5 mL) and phosphorus oxychloride (4.6, 30 mmol) was added. The mixture was heated to reflux overnight. After cooled to rt, the reaction mixture was concentrated. The residue was basified with saturated NaHCO3 solution and extracted with CH2Cl2. The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (0.5% MeOH in CH2Cl2) to give the title compound (1-3). LRMS m/z (M+H) Calcd: 288.7, found: 288.2.

Provenance & Evidence