2-Aminothiazole → 2-(4-bromo-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide

Temperature

0 °C

A solution of 2-(4-bromo-phenyl)-3-cyclopentyl-propionic acid (1.01 g, 3.39 mmol) in methylene chloride (8.5 mL) was treated with 2 drops of dry N,N-dimethylformamide. The reaction mixture was cooled to 0° C. and then treated with oxalyl chloride (3 mL, 33.98 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 15 h. The reaction mixture was concentrated in vacuo. The resulting yellow oil was dissolved in a small amount of methylene chloride and slowly added to a cooled solution (0° C.) of 2-aminothiazole (680.6 mg, 6.79 mmol) and N,N-diisopropylethylamine (1.2 mL, 6.79 mmol) in methylene chloride (17 mL). The resulting reaction mixture was stirred at 0° C. for 10 min and then at 25° C. for 15 h. The reaction mixture was concentrated in vacuo to remove methylene chloride. The resulting residue was diluted with ethyl acetate (200 mL). The organic phase was washed with a 10% aqueous hydrochloric acid solution (2×100 mL), washed with a saturated aqueous sodium bicarbonate solution (2×100 mL), and washed with a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to afford 2-(4-bromo-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (1.23 g, 95%) as an orange solid which was used in subsequent reactions without further purification. An analytical sample was recrystallized from ethyl acetate to provide a cream solid: mp 201-202° C.; EI-HRMS m/e calcd for C17H19BrN2OS (M+) 378.0401, found 378.0405.

1. stirringstirred at 25° C. for 15 h
2. concentrationThe reaction mixture was concentrated in vacuo
3. dissolutionThe resulting yellow oil was dissolved in a small amount of methylene chloride
4. customThe resulting reaction mixture
5. stirringwas stirred at 0° C. for 10 min
6. waitat 25° C. for 15 h
7. concentrationThe reaction mixture was concentrated in vacuo
8. customto remove methylene chloride
9. additionThe resulting residue was diluted with ethyl acetate (200 mL)
10. washThe organic phase was washed with a 10% aqueous hydrochloric acid solution (2×100 mL)
11. washwashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
12. washwashed with a saturated aqueous sodium chloride solution (1×100 mL)
13. dry with materialThe organic layer was then dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-b96025d65635428db340246f794b5ba2

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06320050B1