A process for the preparation of crystalline form a of n, n'-bis(2-aminoethyl)-1,2-ethanediamine tetrahydrochloride

A process for the preparation of crystalline form A of Trientine Tetrahydrochloride (1),

• wherein the process comprising:
• a) adding of 2-chloroacetonitrile (VI)
• to ethane-1,2-diamine (V)
• in the presence of a base to form 2,2′-(ethane-1,2-diylbis(azanediyl)) diacetonitrile (IV);
• b) protecting the free amino groups using suitable protecting groups to obtain the Boc protected Di-tert-butyl ethane-1,2-diylbis(cyanomethyl carbamate) (III);
• c) reducing intermediate (III) by hydrogenation using Raney nickel in the presence of methanolic ammonia and converting to difumarate salt by using fumaric acid to yield Boc protected Di-tert-butyl ethane-1,2-diylbis(2-aminoethylcarbamate) difumarate (II);
• d) deprotecting intermediate (II) by treating with concentrated hydrochloric acid to yield Trientine tetrahydrochloride crude (Ia);
• and
• e) purifying crude Trientine tetrahydrochloride (Ia) to obtain crystalline form A of Trientine Tetrahydrochloride (I), wherein the purification process comprises:
• 1. dissolving crude Trientine tetrahydrochloride (Ia) in a protic solvent,
• 2. heating the reaction mass of step 1), optionally adding anti-solvent, and
• 3. isolating crystalline form A of Trientine tetrahydrochloride.