Diisopropylethylamine → Ethyl 4-chloro-6-((3-ethoxy-3-oxopropyl)(phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate

Temperatur

100 °C

To a solution of ethyl 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylate (47.0 g, 175.94 mmol) in DMF (470 mL) and diisopropylethylamine (100.43 mL, 582.7 mmol) was added ethyl 3-(phenylamino)propanoate (31.0 g, 160.4 mmol). The reaction mixture was heated to 100° C. and stirred for 7 h. Upon completion of the reaction (monitored by TLC), DMF was evaporated under reduced pressure and water (250 mL) was then added. The reaction mixture was extracted using EtOAc (200 mL×3). The combined organic layer was washed with water (500 mL×2), brine (500 mL), dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (using 0-20% Ethyl acetate in hexane) to afford ethyl 4-chloro-6-((3-ethoxy-3-oxopropyl)(phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (55 g, 80.8% yield). 1H NMR (400 MHz, CDCl3): δ 7.38 (t, J=8.0 Hz, 2H), 7.31 (d, J=7.6 Hz, 1H), 7.18 (d, J=7/2 Hz, 2H), 4.26 (t, J=7.6 Hz, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.47 (q, J=7.2 Hz, 2H), 2.68 (t, J=7.6 Hz, 2H), 2.54 (s, 3H), 1.19 (t, J=7.2 Hz, 3H), 1.08 (t, J=7.2 Hz, 3H). LCMS [M+H]; 424

1. customwas evaporated under reduced pressure and water (250 mL)
2. additionwas then added
3. extractionThe reaction mixture was extracted
4. washThe combined organic layer was washed with water (500 mL×2), brine (500 mL)
5. dry with materialdried over anhydrous sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto give a residue
9. customThe residue was purified by silica gel column chromatography (using 0-20% Ethyl acetate in hexane)

ORD-Eintrag

ord-54dc80ad94a6471791d7fa54a85b6333

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08343983B2