Methanol → 2-Tert-butyl-4-[(3-methoxypropyl)amino]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid

Temperatur

80 °C

Methyl 2-cyano-3-[(2,2-dimethylpropanoyl)amino]-3-(methylsulfanyl)prop-2-enoate (2.0 g) was dissolved in 3-methoxypropan-1-amine (1.4 g), and the mixture was stirred at 80° C. for 1 hr. Methanol (10 ml) was added to the reaction mixture, and the mixture was refluxed overnight. The solvent was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography. The fraction eluted with ethyl acetate-hexane (0:10→6:4) was concentrated under reduced pressure, and the fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue (1.0 g) was dissolved in methanol (10 ml), lithium hydroxide (0.42 g) and water (2 ml) were added, and the mixture was stirred at 70° C. for 6 hr. The reaction mixture was allowed to cool to room temperature, acidified with 6 N aqueous hydrochloric acid solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object compound (0.51 g).

1. temperaturethe mixture was refluxed overnight
2. concentrationThe solvent was concentrated under reduced pressure
3. washThe fraction eluted with ethyl acetate-hexane (0:10→6:4)
4. concentrationwas concentrated under reduced pressure
5. washthe fraction eluted with ethyl acetate
6. concentrationwas concentrated under reduced pressure
7. dissolutionThe residue (1.0 g) was dissolved in methanol (10 ml)
8. additionlithium hydroxide (0.42 g) and water (2 ml) were added
9. stirringthe mixture was stirred at 70° C. for 6 hr
10. temperatureto cool to room temperature
11. extractionextracted with ethyl acetate
12. washThe extract was washed with saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe solvent was evaporated under reduced pressure

ORD-Eintrag

ord-2cab7388532e4590a2cfdf3b639657ab

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08329691B2