Propanedioic acid, monoethyl ester → HCID 86634786, compound

Temperature

50 °C

A flask was charged with 2-(5-bromo-2-(4-phenethylthiazol-2-ylamino)pyridin-4-yl)acetic acid (0.576 g, 1.377 mmol) and THF (20 mL), and carbonyl diimidazole (0.3014 g, 1.859 mmol) was added. The mixture was heated at 50° C. for 2 hours. In a separate 50 mL scintillation vial, mono-ethyl malonate (0.2845 ml, 2.410 mmol) was dissolved in THF (15 mL) and cooled to 0° C., and isopropyl magnesium chloride (2.410 mL, 4.819 mmol) was added. This second mixture was stirred at ambient temperature for 30 minutes, then heated to 50° C. and stirred another 30 minutes. Both solutions were cooled to 0° C. and the second mixture was added to the first mixture. The combined mixture was stirred at ambient temperature overnight, then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography, eluting with 20% ethyl acetate/hexane to provide the desired product (0.337 g, 46-10% yield) as white solid.

1. additionwas added
2. temperaturecooled to 0° C.
3. temperatureheated to 50° C.
4. stirringstirred another 30 minutes
5. temperatureBoth solutions were cooled to 0° C.
6. additionthe second mixture was added to the first mixture
7. stirringThe combined mixture was stirred at ambient temperature overnight
8. customquenched with saturated ammonium chloride solution
9. extractionextracted with ethyl acetate
10. washThe combined extracts were washed with water and brine
11. customdried
12. customevaporated
13. customThe residue was purified by silica gel chromatography
14. washeluting with 20% ethyl acetate/hexane

ORD record

ord-92ac2a32e06b4e2597398ce69a8edc6a

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022222B2