Process for the preparation of pyrazinone thrombin inhibitor and its intermediates

In a process for the preparation of a compound of formula (I):

• wherein 2,2-difluoro-2-(2-pyridyl)ethylamine or its salt is reacted with ethyl 3-chloropyrazin(1H)-2-one-1-acetate to form ethyl 3 -(2,2-difluoro-2-(2-pyridyl)ethylamino)-pyrazin(1H)-2-one- 1-acetate, which is chlorinated to form:
• which is further reacted with 2-aminomethyl-3-fluoropyridine or its salt to form 3-fluoro-2-pyridylmethyl-3 -(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-chloropyrazin-2-one- 1 -acetamide, the compound of formula (I), the improvement comprising:
• reducing 2-cyano-3-fluoropyridine with Raney Nickel in the presence of an acid to form 2-aminomethyl-3-fluoropyridine or its salt;
• reacting 2,2-difluoro-2-pyridin-2-ylethanol with 4-toluenesulfonyl chloride to form 2,2-difluoro-2-pyridin-2-ylethyl 4-methylbenzenesulfonate, which is converted to 2,2-difluoro-2-(2-pyridyl)ethylamine or its salt by reacting with ammonia;
• and
• optionally purifying the compound of formula (I) by addition of an organic solvent.