Pyridine → 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-bromo-pyrazin-2-yl-propionamide

Temperature

0 °C

A solution of triphenylphosphine (5.75 g, 21.7 mmol) in anhydrous methylene chloride (35 mL) under argon at 0° C. was treated with N-bromosuccinimide (3.86 g, 21.7 mmol). The mixture was allowed to stir for 15 min at 0° C. and then was treated with 3-cyclopentyl-2(R)-(4-methanesulfonylphenyl)-propionic acid (4.95 g, 16.7 mmol). The resulting mixture was then allowed to warm to 25° C. for 10 min. At this time, 2-amino-5-bromopyrazine (5.81 g, 33.4 mmol) was added, followed by the slow addition of pyridine (5.5 mL, 68.0 mmol). This mixture was allowed to stir for 3 h at 25° C., at which time, the reaction was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed sequentially with a 1N aqueous hydrochloric acid solution (150 mL), a 10% aqueous potassium carbonate solution (100 mL), and a saturated aqueous sodium chloride solution (250 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 75S, Silica, 2.5% to 5% gradient ethyl acetate/methylene chloride) afforded 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-bromo-pyrazin-2-yl-propionamide (6.12 g, 81%) as a light yellow solid.

1. temperatureto warm to 25° C. for 10 min
2. stirringto stir for 3 h at 25° C., at which time
3. concentrationthe reaction was concentrated in vacuo
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed sequentially with a 1N aqueous hydrochloric acid solution (150 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-fef3d3c4885c482da2c0d3c752a87465

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132425B2