Pyridine → HCID 21051841, compound

Temperature

0 °C

A solution of 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid (67 mg, 0.20 mmol) in methylene chloride (5 mL) was treated with N,N-dimethylformamide (3 drops) and then cooled to 0° C. The reaction mixture was then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.11 mL, 0.22 mmol). The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to 25° C., and then was concentrated in vacuo to remove solvents and excess oxalyl chloride. The resulting residue was re-dissolved in dry tetrahydrofuran (5 mL) and was treated dropwise with a solution of 2-aminopyrazine (57 mg, 0.60 mmol) in tetrahydrofuran (2 mL) and pyridine (0.065 mL, 0.80 mmol). The resulting reaction mixture was stirred at 25° C. for 1.5 h. The reaction mixture was then diluted with water (50 mL) and extracted with methylene chloride (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 1/1 hexanes/ethyl acetate) afforded 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-furan-2(R)-yl)-propionamide (51 mg, 61%) as a colorless gum: EI-HRMS m/e calcd for C19H20F3N3O2S (M)+ 411.1228, found 411.1229.

1. temperatureto warm to 25° C.
2. concentrationwas concentrated in vacuo
3. customto remove solvents and excess oxalyl chloride
4. dissolutionThe resulting residue was re-dissolved in dry tetrahydrofuran (5 mL)
5. customThe resulting reaction mixture
6. stirringwas stirred at 25° C. for 1.5 h
7. extractionextracted with methylene chloride (3×50 mL)
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-699fa0c2bdd84df9b152da549af468b7

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2