Hydrochloric Acid → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-quinolin-2-yl-propionamide

Temperature

0 °C

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 26, 125 mg, 0.389 mmol) in methylene chloride (3 mL) was treated with N,N-dimethylformamide (1 drop) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.051 mL, 0.583 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a solution of 2-aminoquinoline (84 mg, 0.583 mmol) and triethylamine (0.108 mL, 0.778 mmol) in N, N-dimethylformamide (2 mL). The resulting reaction mixture was stirred at 25° C. for 20 h. The reaction mixture was then diluted with water (25 mL), a 1N aqueous hydrochloric acid solution (5 mL), and ethyl acetate (25 mL). The layers were separated, and the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-quinolin-2-yl-propionamide (50.6 mg, 30%) as an off-white foam: mp 95-99° C. (foam to gel); EI-HRMS m/e calcd for C25H25N3O3S (M+) 447.1617, found 447.1616.

1. customThe resulting reaction mixture
2. temperatureto warm to 25° C. where it
3. concentrationThe reaction mixture was then concentrated in vacuo
4. additionThe resulting yellow gel was diluted with methylene chloride (2 mL)
5. customThe resulting reaction mixture
6. stirringwas stirred at 25° C. for 20 h
7. customThe layers were separated
8. dry with materialthe organic layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-5133abfdc54e48bdb3ff2149d7e5f063

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06448399B1