Dicyclohexylcarbodiimide → 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-[1,2,4]triazin-3-yl-propionamide

Temperature

25 °C

A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared in Example 38, 400 mg, 1.40 mmol) in dry pyridine (5 mL) was treated with 1,3-dicyclohexylcarbodiimide (316 mg, 1.53 mmol). The reaction mixture was stirred at 25° C. for 3.5 h and then treated with 3-amino-1,2,4-triazine (296 mg, 3.08 mmol) and an additional amount of pyridine (1 mL). The reaction mixture was warmed at 100° C. for 20 h. The reaction mixture was concentrated in vacuo to remove pyridine. The resulting residue was diluted with ethyl acetate then filtered. The filtrate was washed with a 1N aqueous hydrochloric acid solution and washed with water. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-[1,2,4]triazin-3-yl-propionamide (40.9 mg, 8%) as a yellow-orange solid: mp 81-83° C.; EI-HRMS m/e calcd for C17H18Cl2N4O (M+) 364.0858, found 364.0857.

1. temperatureThe reaction mixture was warmed at 100° C. for 20 h
2. concentrationThe reaction mixture was concentrated in vacuo
3. customto remove pyridine
4. additionThe resulting residue was diluted with ethyl acetate
5. filtrationthen filtered
6. washThe filtrate was washed with a 1N aqueous hydrochloric acid solution
7. washwashed with water
8. dry with materialThe organic layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-d367f8e086d2491c85ceea410d1e192f

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06320050B1