Large Scale Preparation of Protected 4-Aminomethylbenzamidine. Application to The Synthesis of the Thrombin Inhibitor, Melagatran

To allow the preparation of melagatran on a multigram scale, we have investigated several approaches for the synthesis of the key intermediate 4-aminomethylbenzamidine. The only industrially suitable pathway relies on the preparation of an N-hydroxyimino intermediate.