2-Aminothiazole → (E)-3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-acrylamide

Temperature

0 °C

A solution of triphenylphosphine (8.79 g, 33.52 mmol) in methylene chloride (100 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (5.97 g, 33.52 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-3-cyclohexyl-2-(4-(methanesulfonyl)-phenyl)-acrylic acid (5.17 g, 16.76 mmol) in methylene chloride (20 mL). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (5.04 g, 50.3 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (250 mL) and a 1N aqueous hydrochloric acid solution (150 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×100 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×250 mL), dried over anhydrous magnesium sulfate, filtered, and, concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 8.5/1.5 to 3/2 hexanes/ethyl acetate) afforded (E)-3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-acrylamide (2.8 g, 42%) as an amorphous solid: mp 167-1694° C.; EI-HRMS m/e calcd for C19H22O3S2 (M+) 390.1072, found 390.1073.

1. stirringThe clear solution was stirred for 15 min at 0° C.
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 1.5 h
4. stirringthe resulting suspension was stirred for 2 d at 25° C
5. concentrationThe reaction mixture was concentrated in vacuo
6. customto remove methylene chloride
7. additionthe residue was diluted with ethyl acetate (250 mL)
8. customThe two layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (1×100 mL)
10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×150 mL)
11. dry with materiala saturated aqueous sodium chloride solution (1×250 mL), dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-61278960f45444df86afa7a4cf3d8825

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1