2-Aminothiazole → (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid thiazol-2-ylamide

Temperature

0 °C

A solution of triphenylphosphine (672 mg, 2.56 mmol) in methylene chloride (7.5 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (456 mg, 2.56 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid (545.5 mg, 1.47 mmol) in methylene chloride (4 mL). The clear solution was stirred for 10 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then treated with 2-aminothiazole (378 mg, 3.76 mmol), and the resulting suspension was stirred at 25° C. over the weekend. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (75 mL) and a 1N aqueous hydrochloric acid solution (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×50 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 to 1/1 hexanes/ethyl acetate) afforded (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid thiazol-2-ylamide (200 mg, 35%) as a white solid: mp 173-176° C.; EI-HRMS m/e calcd for C19H22N2O3S2 (M+) 390.1071, found 390.1072.

1. stirringThe clear solution was stirred for 10 min at 0° C.
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 1 h
4. stirringthe resulting suspension was stirred at 25° C. over the weekend
5. concentrationThe reaction mixture was concentrated in vacuo
6. customto remove methylene chloride
7. additionthe residue was diluted with ethyl acetate (75 mL)
8. customThe two layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (1×50 mL)
10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL)
11. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-2bf85298741040deb2936593f3693a4e

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1