Reaktion #366064

Reaktionsgleichung

hydrogen chloride

2-(2-amino-4-methyl-pentylamino)-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide

hexahydroazepinyl carbamoyl chloride

N,N-diisopropylethylamine

benzene

→

title compound

Azepane-1-carboxylic acid (1-{[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethylamino]-methyl}-3-methyl-butyl)-amide dihydrochloride salt

Lösungsmittel

ethyl acetate

diethyl ether

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturunder reflux for 16 hours
2. 2
   Filtrationfiltered
3. 3
   Waschenthe solids washed with benzene
4. 4
   EinengenThe filtrate was concentrated under reduced pressure
5. 5
   Sonstigethe residue thus obtained
6. 6
   Waschenwashed with 100 mL each saturated NaHCO3 solution and brine
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   Sonstigeto give a pale amber oil that
10. 10
    Sonstigewas purified by column chromatography on silica gel with 1:1 ethyl acetate
11. 11
    SonstigeThe clear, colorless oil obtained
12. 12
    SonstigeThe precipitate that formed
13. 13
    Filtrationwas collected by filtration
14. 14
    Waschenthe solids washed with ethyl acetate
15. 15
    Sonstigedried

Vorschrift

A solution of 746 mg (1.6 mmol) 2-(2-amino-4-methyl-pentylamino)-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide, 0.408 mL (3.1 mmol) hexahydroazepinyl carbamoyl chloride, 20 mg (0.16 mmol) 4-dimethylaminopyridine (Aldrich, Milwaukee, Wis.), 0.818 mL (4.7 mmol) N,N-diisopropylethylamine (Aldrich, Milwaukee, Wis.), in 10 mL of benzene was heated under reflux for 16 hours, cooled to 25° C. and filtered, and the solids washed with benzene. The filtrate was concentrated under reduced pressure, and the residue thus obtained was dissolved in 100 mL ethyl acetate, and washed with 100 mL each saturated NaHCO3 solution and brine, dried over anhydrous magnesium sulfate, then concentrated under reduced pressure to give a pale amber oil that was purified by column chromatography on silica gel with 1:1 ethyl acetate:chloroform as eluant. The clear, colorless oil obtained was dissolved in 10 mL diethyl ether, and treated with diethyl ether that had been saturated with hydrogen chloride gas. The precipitate that formed was collected by filtration, and the solids washed with ethyl acetate and dried. The title compound was obtained as 440 mg off-white solid (77%); mp 51-57° C.

Quelle