Methanol → Methyl 6-chloro-2-(methylsulfanyl)pyrimidine-4-carboxylate

Temperatur

0 °C

A 250 mL flask was charged with 2-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid (11.6 g, 62.5 mmol), toluene (60 mL), thionyl chloride (60 mL, 0.8 mol, 13 eq.), DMF (0.3 mL), and pyridine (1 mL), and the resultant stirred suspension was heated to reflux. The suspension clarified after 30 min. After 3 hours at reflux, the mixture was concentrated in vacuo, and co-evaporated with additional toluene (30 mL). The biphasic brown residue was dissolved in chloroform (100 mL), cooled to 0° C., and DIEA (56 mL, 0.31 mol, 5 eq.) added dropwise over 20 min followed by methanol (12.7 mL, 0.31 mol, 5 eq.) over 5 min. The mixture was warmed to room temperature, and poured into saturated aqueous sodium bicarbonate (350 mL). The organic layer was washed with saturated aqueous ammonium chloride (350 mL), dried (Na2SO4), filtered, and concentrated in vacuo to a brown semi-solid. Overnight drying under high vacuum afforded 6-chloro-2-methylsulfanyl-pyrimidine-4-carboxylic acid methyl ester that was taken to the next step without further purification. 1H NMR (500 MHz, CDCl3) □ 7.60 (s, 1H), 3.98 (s, 3H), 2.60 (s, 3H); ESI-MS m/z 218.9 (M+H)+.

1. temperaturewas heated to reflux
2. temperatureAfter 3 hours at reflux
3. concentrationthe mixture was concentrated in vacuo
4. dissolutionThe biphasic brown residue was dissolved in chloroform (100 mL)
5. temperatureThe mixture was warmed to room temperature
6. washThe organic layer was washed with saturated aqueous ammonium chloride (350 mL)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo to a brown semi-solid
10. customOvernight drying under high vacuum

ORD-Eintrag

ord-9367893867004a7185073ae741d60f2d

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822451B2