تفاعل #95985

معادلة التفاعل

N-methyl-morpholine

chloroformic acid isobutyl ester

agmatine-dichlorohydrate

triethylamine

benzyloxycarbonyl-D-phenylalanyl-L-proline

→

Benzyloxycarbonyl-D-phenylalanyl-L-prolyl-agmatine-chlorohydrate

المذيبات

water

dimethylformamide

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONare added
2. 2
   workup.ADDITIONwhen the following solution is poured into it
3. 3
   درجة الحرارةcooled to -15° C
4. 4
   workup.STIRRINGThe reaction mixture is stirred for 2 hours at -15° C., for 1 hour
5. 5
   درجة الحرارةwithout cooling
6. 6
   أخرىis evaporated at reduced pressure
7. 7
   workup.DISSOLUTIONThe evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid
8. 8
   استخلاصextracted three times with 20 ml of ethyl acetate
9. 9
   استخلاصextracted five times with 20 ml of chloroform
10. 10
    غسيلThe combined chloroform layers are washed twice with 10 ml of water
11. 11
    أخرىevaporated at reduced pressure
12. 12
    ترشيحfiltered
13. 13
    غسيلwashed with diethyl ether
14. 14
    أخرىair-dried

الإجراء التجريبي

4 g (10 mmoles) of benzyloxycarbonyl-D-phenylalanyl-L-proline (Nikolaides et al.: J.Med.Chem., 11, 74, 1968) are dissolved in 20 ml of dimethylformamide, cooled to -15° C., and at this temperature and constant stirring 1.11 ml (10 mmoles) of N-methyl-morpholine and 1.32 ml (10 mmoles) of chloroformic acid isobutyl ester are added. Stirring is continued for 10 minutes when the following solution is poured into it: 2.05 g (10 mmoles) of agmatine-dichlorohydrate (in formula II A means an H2N--C(NH)-- residue, B a chlorine atom and n=2) are suspended in 15 ml of dimethylformamide, 2 ml of water, then 1.4 ml (10 mmoles) of triethylamine are added, and cooled to -15° C. The reaction mixture is stirred for 2 hours at -15° C., for 1 hour without cooling, then is evaporated at reduced pressure. The evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid and extracted three times with 20 ml of ethyl acetate. The pH of the aqueous layer is adjusted with solid sodium hydrogen carbonate to 8.0 to 8.5, and extracted five times with 20 ml of chloroform. The combined chloroform layers are washed twice with 10 ml of water, and evaporated at reduced pressure. The residue is worked up with diethyl ether, filtered, washed with diethyl ether and air-dried. Yield: 4.1 g (75 percent) of the named compound. RF3 0.5 to 0.6.

المصدر