Pyridine → HCID 10073865, compound

Temperature

5 °C

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 200 mg, 0.604 mmol) in methylene chloride (5 mL) and N,N-dimethylformamide (2 drops) was cooled to 5° C. and then treated with oxalyl chloride (105 μL, 1.2 mmol). The solution was stirred at 5° C. for 5 min, the cooling bath was removed, and the stirring was continued for 10 min. At this time, the reaction mixture was concentrated in vacuo, the residue was dissolved in benzene (10 mL), and the solvent was concentrated in vacuo again. The resulting acid chloride was dissolved in methylene chloride (5 mL), cooled to 5° C., and then treated with a solution of 5-[1,3]dioxolan-2-yl-pyrazin-2-ylamine (105 μL, 0.628 mmol), pyridine (100 μL, 1.23 mmol) in methylene chloride (5 mL). After 5 min, the cooling bath was removed, and the stirring was continued for 18 h. The reaction mixture was then diluted with methylene chloride (50 mL), and the solution was washed with a saturated aqueous sodium bicarbonate solution (25 mL), a 0.5M aqueous hydrochloric acid solution (25 mL), and a saturated aqueous sodium chloride solution (25 mL). Each aqueous wash was extracted with a small portion of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford a yellow oil. Flash chromatography (Merck Silica gel 60, 230–400 mesh, various concentrations of ethyl acetate/hexanes) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-[1,3]dioxolan-2-yl-pyrazin-2-yl)-propionamide (148 mg, 51%) as a colorless foam: (ES)+-HRMS m/e calcd for C22H26ClN3O5S (M+H)+ 480.1355, found 480.1357.

1. customthe cooling bath was removed
2. waitthe stirring was continued for 10 min
3. concentrationAt this time, the reaction mixture was concentrated in vacuo
4. dissolutionthe residue was dissolved in benzene (10 mL)
5. concentrationthe solvent was concentrated in vacuo again
6. dissolutionThe resulting acid chloride was dissolved in methylene chloride (5 mL)
7. temperaturecooled to 5° C.
8. waitAfter 5 min
9. customthe cooling bath was removed
10. waitthe stirring was continued for 18 h
11. additionThe reaction mixture was then diluted with methylene chloride (50 mL)
12. washthe solution was washed with a saturated aqueous sodium bicarbonate solution (25 mL)
13. washEach aqueous wash
14. extractionwas extracted with a small portion of methylene chloride
15. dry with materialThe combined organic layers were dried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customto afford a yellow oil
19. concentrationFlash chromatography (Merck Silica gel 60, 230–400 mesh, various concentrations of ethyl acetate/hexanes)

ORD record

ord-762790b8ea3d458a9e3b2beb2cb35162

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132425B2