Triphenylphosphine → (E)-2-[4-Cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoylamino]-thiazole-5-carboxylic acid ethyl ester

온도

0 °C

A solution of triphenylphosphine (787 mg, 3 mmol) in methylene chloride (40 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (534 mg, 3 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid (prepared in Example 21, 462 mg, 1.5 mmol). 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-5-carboxylic acid ethyl ester (774 mg, 4.5 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 (70 mL) and a 1N aqueous hydrochloric acid solution (70 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 (1×100 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, 3/1 to 1/1 hexanes/ethyl acetate) afforded (E)-2-[4-Cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoylamino]-thiazole-5-carboxylic acid ethyl ester (250 mg, 36%) as an amorphous white solid: ET-HRMS m/e calcd for C22H26N2O5S2 (M+) 462.1283, found 462.1282.

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 (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 saturated aqueous sodium bicarbonate solution (1×100 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 기록

ord-daba422ce9b54c21a41d7078152a30ea

출처 데이터셋

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06353111B1