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

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 (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. LRMS m/z (M+H) Calcd: 288.7, found: 288.2.

1. stirringThe mixture was stirred
2. customThe reaction was quenched with saturated NH4Cl solution
3. extractionextracted with CH2Cl2
4. customThe combined organic layer was dried
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in CH3CN (5 mL)
8. temperatureThe mixture was heated
9. temperatureto reflux overnight
10. temperatureAfter cooled to rt
11. concentrationthe reaction mixture was concentrated
12. extractionextracted with CH2Cl2
13. customThe combined organic layer was dried
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was purified by silica gel chromatography (0.5% MeOH in CH2Cl2)

ORD record

ord-21d879118c8a44e887d10964fc14cc0b

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07544677B2