Triphenylphosphine → HCID 10138675, compound

Temperature

0 °C

A solution of triphenylphosphine (525 mg, 2 mmol) in methylene chloride (25 mL) was cooled to 0° C. and then treated with N-bromosuecinimide (355 mg, 2 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, 308 mg, 1 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-4-carboxylic acid methyl ester (400 mg, 2.52 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 (50 mL) and a 1N aqueous hydrochloric acid solution (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×25 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, 3/1 to 1/1 hexanes/ethyl acetate) afforded (E)-2-[4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoylamino]-thiazole-4-carboxylic acid methyl ester (250 mg, 56%) as a white solid: mp 85-90° C.; EI-HRMS m/e calcd for C21H24N2O5S2 (M+) 448.1127, found 448.1117.

1. additiontreated with N-bromosuecinimide (355 mg, 2 mmol)
2. stirringThe clear solution was stirred for 10 min at 0° C.
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 1 h
5. stirringthe resulting suspension was stirred at 25° C. over the weekend
6. concentrationThe reaction mixture was concentrated in vacuo
7. customto remove methylene chloride
8. additionthe residue was diluted with ethyl acetate (50 mL)
9. customThe two layers were separated
10. extractionthe aqueous layer was extracted with ethyl acetate (1×25 mL)
11. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL)
12. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-627b9de122094c9587cc0f226620f0c6

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1