2-Aminothiazole → 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide

Temperature

25 °C

A solution of 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-propionic acid (380 mg, 1.4 mmol), in methylene chloride (4 mL) and N,N-dimethylformamide (1 drop) at 0° C. was treated with oxalyl chloride (1.22 mL, 14.0 mmol). The reaction was warmed to 25° C. and stirred at 25° C. for 18 h. At this time, the reaction mixture was concentrated in vacuo. The resulting residue was dissolved in methylene chloride (4 mL) and added to a solution of 2-aminothiazole (280 mg, 2.79 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.87 mmol) in methylene chloride (8 mL) at 25° C. The reaction was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was poured into a 0.5N aqueous hydrochloric acid solution (50 mL) and extracted into ethyl acetate (1×100 mL). The organic extract was washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a half-saturated aqueous sodium chloride solution (1×50 mL). The aqueous layer was back extracted with ethyl acetate (1×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate) afforded the 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide (159 mg, 72%) as an off-white solid: mp 220-222° C.; EI-HRMS m/e calcd for C20H22N2O2S (M+) 354.1402, found 354.1388.

1. concentrationAt this time, the reaction mixture was concentrated in vacuo
2. dissolutionThe resulting residue was dissolved in methylene chloride (4 mL)
3. stirringThe reaction was stirred at 25° C. for 18 h
4. concentrationAt this time, the reaction was concentrated in vacuo
5. additionThe residue was poured into a 0.5N aqueous hydrochloric acid solution (50 mL)
6. extractionextracted into ethyl acetate (1×100 mL)
7. extractionThe organic extract
8. washwas washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
9. extractionThe aqueous layer was back extracted with ethyl acetate (1×100 mL)
10. dry with materialThe combined organic extracts were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-17e6a560736c4af1b1524d21a6016e2a

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06388071B2