Dicyclohexylcarbodiimide → HCID 178513959, compound

Participants

Reaction Conditions

Reaction Steps

4.8 g of 5-chloro orotic acid, 3.6 g of 1-hydroxybenzotriazole and L-histidyl-L-prolinamide dihydrobromide (prepared from 9.7 g N-benzyloxycarbonyl-L-histidyl-L-prolinamide as described in Example 2) are mixed with 150 ml of dimethylformamide. After chilling to -5° C. while stirring 7.0 ml of triethylamine and then the solution of 5.2 g of N,N'-dicyclohexylcarbodiimide in 20 ml of dimethylformamide are added. Under continuous stirring the mixture is stored for 90 minutes at -5° to 0° C. and thereafter for 24 hours, during which time it is allowed to warm to room temperature. The precipitate formed is separated by filtration and the filtrate is evaporated under reduced pressure at a temperature of about 35° C. The residue is treated with 75 ml of water, stored for 12 hours at 0° C. and filtered. The filtrate is stirred for 10 minutes with 75 g of a cationic exchanger in the free acid form (as, for instance, the product named in Example 2). After separating the resin it is washed four times with 250 ml of water each and four times with 50 ml of methanol each. Then the cationic exchanger resin is suspended in 100 ml of water, while stirring treated with 120 ml of 1n ammonia, sucked off and washed six times with 20 ml of 1n ammonia each. The combined ammoniacal filtrates are, at about 35° C. under reduced pressure, evaporated to a small volume and finally lyophylized. The residue is two times recrystallized from water/ethanol (1:1) and thereafter dried in vacuum over phosphorus pentoxide. Thus, 4.7 g (44.8% of the theoretical yield) of 5-chloro-orotyl-L-histidyl-L-prolinamide, melting at 204° - 206° C. are obtained.

Provenance & Evidence