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

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Reaction Steps

To a solution of methyl phenylacetate (15.5 mL, 110 mmol) in THF (300 mL) at −78° C. was added LHMDS (1 M, 120 mL, 2.3 mmol) and stirred for 1 hr. 4-amino-2-(ethylthio)pyrimidine-5-carbaldehyde (6-2) (9.6 g, 52 mmol) was added. The mixture was warmed to room temperature and stirred for 12 hr. The reaction was quenched with saturated NH4Cl solution and extracted with CH2Cl2. The combined organic layer was dried, filtered and concentrated. The resulting solid was triturated with Et2O and the white purified solid was filtered. A portion of the solid (2.5 g, 8.8 mmol) was dissolved in CH3CN and phosphorus oxychloride (8.0 mL, 88 mmol) was added. The mixture was heated to reflux for 12 hr. After 12 hr, the solvent and POCl3 were distilled off using a dean stark apparatus until 15 mL remained in the flask. Upon cooling, a white solid formed and was filtered. The solid washed with Et2O and dried under vacuum to afford the salt of (6-3). The mother liquor was basified by slowly adding Et3N dropwise until pH=7, diluted with water, and extracted with CH2Cl2. The combined organic layer was dried, filtered and concentrated. The residue was purified by trituration with Et2O and filtered to yield pure (6-3) as a free base. LRMS m/z (M+H) Calcd: 302.0, found: 302.0.

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