Dicyclohexylcarbodiimide → HCID 178429388, compound

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Reaction Steps

To 100 ml of dimethylformamide are added, while stirring at room temperature, 17.0 g of 5-methyl orotic acid, 14.4 g of 1-hydroxybenzotriazole and 27.8 ml of triethylamine. After 10 minutes the mixture is chilled in an ice bath and 10 minutes later a solution of 20.6 g of N,N'-dicyclohexyl-carbodiimide in 30 ml of dimethylformamide and then L-histidyl-L-prolinamide dihydrobromide (obtained as described in Example 2 from 38.5 g of N-benzyloxycarbonyl-L-histidyl-L-prolinamide) and a further amount of 100 ml of dimethylformamide are added. The mixture is stirred for 30 minutes in the ice bath and then for 12 hours at room temperature and thereafter worked up as described in Example 2 until and including the preliminary purification with a cationic exchanger. The residue of the ammoniacal solution is recrystallized from 110 ml of ethanol. After chilling for 24 hours to 0° C. the product is filtrated by suction and dried over phosphorous pentoxide. 2 g portions of this material are dissolved in methanol/water (1:1) and chromatographed over a column of 350 g basic aluminium oxide. The elution is controlled by measuring the ultraviolet absorption spectrum at 254 nm and the fractions containing the pure main product are combined and evaporated under reduced pressure. The residue is dissolved in methanol, filtered, evaporated to dryness, redissolved in water and lyophylized. Thus, 14.4 g (30.4% of the theoretical yield) of 5-methyl-orotyl-L-histidyl-L-prolinamide trihydrate melting at 222° - 227° C. with decomposition are obtained.

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