Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-propionamide

Temperature

0 °C

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 1.59 g, 4.805 mmol) in methylene chloride (24 mL) and N,N-dimethylformamide (2 drops) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (855 μL, 9.609 mmol). The reaction mixture was stirred at 0° C. for 30 min and then warmed to 25° C. where it was stirred for 2 h. The solution was then concentrated in vacuo. The yellow slurry was dissolved in methylene chloride (24 mL) and then cooled to 0° C. To this solution was added a solution of 5-(1,1-dimethoxy-ethyl)-pyrazin-2-ylamine (880.4 mg, 4.805 mmol) and pyridine (466 μL, 5.766 mmol) in methylene chloride (24 mL). The reaction mixture was stirred at 0° C. for 1 h. The reaction was then quenched with a saturated aqueous sodium chloride solution (50 mL), and the layers were separated. The aqueous layer was back-extracted with methylene chloride (50 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (75 mL), an aqueous copper(II) sulfate solution (2×50 mL), and a saturated aqueous sodium chloride solution (75 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 3/7 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-propionamide (1.25 g, 52%) as a white foam: mp 85–88° C. (foam to gel); (ES)+-HRMS m/e calcd for C23H30ClN3O5S (M+Na)+ 518.1487, found 518.1488.

1. temperaturewarmed to 25° C. where it
2. stirringwas stirred for 2 h
3. concentrationThe solution was then concentrated in vacuo
4. dissolutionThe yellow slurry was dissolved in methylene chloride (24 mL)
5. temperaturecooled to 0° C
6. stirringThe reaction mixture was stirred at 0° C. for 1 h
7. customThe reaction was then quenched with a saturated aqueous sodium chloride solution (50 mL)
8. customthe layers were separated
9. extractionThe aqueous layer was back-extracted with methylene chloride (50 mL)
10. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (75 mL)
11. dry with materialan aqueous copper(II) sulfate solution (2×50 mL), and a saturated aqueous sodium chloride solution (75 mL), dried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-5e2bc7d2c11342939031372c38941eca

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132425B2