MRA-CN is a byproduct of the synthesis of 3'-deamino-3'-(4-morpholinyl)doxorubicin (III) by the reductive alkylation of doxorubicin (I) with 2,2'-oxybisacetaldehyde (II) and NaBH3CN (I). An iminium intermediate in this process evidenly undergoes nucleophilic attack by cyanide ion present in the reaction mixture, in competition with the normal attack by hydride. Unlike the expected morpholino derivative (III) (and most anthracyclines), MRA-CN is nonbasic. It remains in the organic layer (e.g., chloroform) when the morpholino derivative is extracted with dilute aqueous acid. MRA-CN is then recovered from the organic layer and purified by chromatography on silica gel using gradient elution with dichloromethane-methanol. Yields range from 15% to 40%. MRA-CN does not form an HCl salt.

MRA-CN is a byproduct of the synthesis of 3'-deamino-3'-(4-morpholinyl)doxorubicin (III) by the reductive alkylation of doxorubicin (I) with 2,2'-oxybisacetaldehyde (II) and NaBH3CN (I). An iminium intermediate in this process evidenly undergoes nucleophilic attack by cyanide ion present in the reaction mixture, in competition with the normal attack by hydride. Unlike the expected morpholino derivative (III) (and most anthracyclines), MRA-CN is nonbasic. It remains in the organic layer (e.g., chloroform) when the morpholino derivative is extracted with dilute aqueous acid. MRA-CN is then recovered from the organic layer and purified by chromatography on silica gel using gradient elution with dichloromethane-methanol. Yields range from 15% to 40%. MRA-CN does not form an HCl salt.