Potassium Carbonate → (2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide

Temperatur

80 °C

(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide was prepared from (2S,4R)-4-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester. (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.40 g, 0.92 mmol) was dissolved in DMF at room temperature and K2CO3 (0.127 g, 0.921 mmol) was added. 4-(3-Chloro-propyl)-piperazine-1-carboxylic acid tert-butyl ester (0.242 g, 0.921 mmol) was added and the reaction was allowed to heat to 80° C. overnight. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water, then extracted three times with ethyl acetate, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography to afford the product as colorless oil in 50% yield. (2S,4R)-4-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester (246 mg) was dissolved in 4M HCl in dioxane (2 mL). The mixture was stirred for 2 h at room temperature. After concentration, the white solid was washed with EtOAc to provide the title compound in 100% yield.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customThe residue was partitioned between ethyl acetate and water
3. extractionextracted three times with ethyl acetate
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated down
7. customThe crude residue was purified by silica gel chromatography

ORD-Eintrag

ord-f453b0676496406c9cd3738e011c6da1

Quelldatensatz

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07504508B2