Dicyclohexylcarbodiimide → HCID 178513958, compound

Participants

Reaction Conditions

Reaction Steps

To 100 ml of dimethylformamide are added 5.1 g of 2-oxo-imidazole-4-carboxylic acid, 5.8 g of 1-hydroxybenzotriazole and L-histidyl-L-prolinamide dihydrobromide (prepared as described in Example 2 from 15.4 g of N-benzyl-oxycarbonyl-L-histidyl-L-prolinamide). After chilling to -5° C. while stirring 11.1 ml of triethylamine and thereafter the solution of 8.3 g of N,N'-dicyclohexylcarbodiimide in 30 ml of dimethylformamide are added. The stirred mixture is chilled for 30 minutes longer and then it is stored for 12 hours at room temperature. The precipitate formed is sucked off and the solution is evaporated under reduced pressure and at a temperature of about 35° C. The residue is mixed with 100 ml of water, stored for 12 hours at 0° C. filtered and then the filtrate is treated with a cationic exchanger and thereafter with 1n ammonia as described in Example 2. The ammoniacal filtrates are combined, evaporated under reduced pressure to a small volume and finally lyophylized. The residue is subjected to countercurrent distribution in the system n-butanol/water. The fractions containing the main product are combined, evaporated to dryness and the residue is dissolved in 50 ml of methanol and reprecipitated by addition of 500 ml of chloroform, which treatment then is repeated once. After drying in vacuum 4.7 g (27% of the theoretical yield) of 2-oxo-imidazole-4-carbonyl-L-histidyl-L-prolinamide trihydrate are obtained. This substance on heating above 180° C. begins to sinter and on heating to 212° C. it is molten.

Provenance & Evidence