Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide

Temperatur

0 °C

A solution of triphenylphosphine (248 mg, 0.94 mmol) in methylene chloride (9 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (190 mg, 1.07 mmol). The reaction mixture was stirred at 0° C. until it was completely dissolved and became light purple in color. The reaction mixture was then treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (208 mg, 0.63 mmol). The reaction mixture was stirred at 0° C. for 20 min and then warmed to 25° C. where it was stirred for 30 min. After such time, the reaction mixture was treated with 2-aminothiazole (95 mg, 0.94 mmol) and pyridine (0.092 mL, 1.13 mmol), and the reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (10 mL) and then extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (210 mg, 81%) as a white foam: [α]23589=−54.3° (c=0.081, chloroform); EI-HRMS m/e calcd for C18H21ClN2O3S2 (M+) 412.0682, found 412.0679.

1. dissolutionwas completely dissolved
2. stirringThe reaction mixture was stirred at 0° C. for 20 min
3. temperaturewarmed to 25° C. where it
4. stirringwas stirred for 30 min
5. stirringthe reaction mixture was stirred at 25° C. for 16 h
6. extractionextracted with methylene chloride (3×15 mL)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-6ab435d2663245b28776ebdeca8e3926

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06610846B1