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

Temperature

0 °C

A solution of triphenylphosphine (720 mg, 2.75 mmol) in methylene chloride (25 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (490 mg, 2.75 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)-3-nitro-phenyl)-acrylic acid (485 mg, 1.37 mmol) in methylene chloride (5 mL). The reaction mixture 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 (412 mg, 4.12 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (70 mL) and a 1N aqueous hydrochloric acid solution (50 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 1N aqueous hydrochloric acid solution (1×100 mL), a saturated aqueous sodium bicarbonate solution (1×100 mL), and a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 5/1 to 3/2 hexanes/ethyl acetate) afforded the (E)-3-cyclohexyl-2-(4-methanesulfonyl-3-nitro-phenyl)-N-thiazol-2-yl-acrylamide (122 mg, 20%) as an amorphous solid: EI-HRMS m/e calcd for C19H21N3O5S2 (M+) 435.0923, found 435.0923.

1. stirringThe reaction mixture 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 then concentrated in vacuo
6. customto remove methylene chloride
7. additionthe residue was diluted with ethyl acetate (70 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 1N aqueous hydrochloric acid solution (1×100 mL)
11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-2f665c93a70e4da6b4963a848783a676

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1