تفاعل #366064

معادلة التفاعل

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

المذيبات

ethyl acetate

diethyl ether

diethyl ether

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةunder reflux for 16 hours
2. 2
   ترشيحfiltered
3. 3
   غسيلthe solids washed with benzene
4. 4
   تركيزThe filtrate was concentrated under reduced pressure
5. 5
   أخرىthe residue thus obtained
6. 6
   غسيلwashed with 100 mL each saturated NaHCO3 solution and brine
7. 7
   تجفيفdried over anhydrous magnesium sulfate
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىto give a pale amber oil that
10. 10
    أخرىwas purified by column chromatography on silica gel with 1:1 ethyl acetate
11. 11
    أخرىThe clear, colorless oil obtained
12. 12
    أخرىThe precipitate that formed
13. 13
    ترشيحwas collected by filtration
14. 14
    غسيلthe solids washed with ethyl acetate
15. 15
    أخرىdried

الإجراء التجريبي

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.

المصدر