4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → HCID 71224526、化合物

To a cold (−78° C.) freshly-prepared solution of lithium diisopropylamide (2.62 mmol) in THF (5 mL) was added a solution of 2-phenyl-2-(trimethylsilyloxy)acetonitrile (0.5 ml, 2.382 mmol) in THF (4 mL). The solution was stirred for 2 hours, and a solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (554 mg, 2.382 mmol) in THF (3 mL) was added dropwise. The cold bath was removed, and the reaction warmed to room temperature. The reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL). The layers were separated, and the aqueous extracted with addition ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in THF (15 mL), and a solution of tetrabutyl ammonium fluoride (3.0 mmol, 3.0 mL, 1 M in THF) was added. The reaction mixture was stirred for 1 hour, and quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL). The layers were separated, and the aqueous layer extracted with addition ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a gradient of hexane to 30% ethyl acetate in hexane, to give the title compound. MS ESI(+) m/z 302.9 [M+H]+.

1. customThe cold bath was removed
2. customThe reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL)
3. customThe layers were separated
4. extractionthe aqueous extracted with addition ethyl acetate
5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe residue was dissolved in THF (15 mL)
9. stirringThe reaction mixture was stirred for 1 hour
10. customquenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL)
11. customThe layers were separated
12. extractionthe aqueous layer extracted with addition ethyl acetate
13. dry with materialThe combined organics were dried with anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by chromatography on silica gel
17. washeluting with a gradient of hexane to 30% ethyl acetate in hexane

ORDレコード

ord-4113655260c44ef8abf97167ad8e9f83

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08796289B2