Methods are provided for the synthesis of key intermediates for the synthesis of Argatroban monohydrate ethyl (2R4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl. Such intermediates are also provided.

The present disclosure is directed to methods of achieving anticoagulation in a patient in need thereof. The typical patient is expected to be in need for anticoagulation treatment for an extended period of time, and therefore has an increased risk of developing heparin resistance. The method comprises administering a therapeutically effective amount of a direct thrombin inhibitor, such as argatroban. The disclosed methods are particularly suited for the treatment of critically ill patients who ...

a polymorphic form of argatroban monohydrate is described. A method is described for preparing argatroban monohydrate obtained from (2 R ,4 R )-1-[N G -nitro-N 2 -(3-methyl-8-quinolinesulphonyl)-L-arginyl]-4-methyl-2-piperidine carboxylic acid by suitably treating crude argatroban. The method either comprises preparation of argatroban monohydrate in a continuous step or an intermediate step of isolating a purified argatroban.