Process and intermediates for the preparation of perampanel

A process for the preparation of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2 dihydro-pyridin-2-one (Perampanel) represented by the structure of formula (1), and salts thereof,

• comprising the following steps:
• a). reacting a compound of formula (2) with a formylating agent to form a compound of formula (3)
• wherein
• Y is OR2 or NR3R4;
• R1, R2, R3 and R4 are each independently a (C1-C4)-alkyl or an aryl;
• and
• X is a group that can be converted to a CN group;
• b). reacting compound (3) with aniline to form a compound of formula (4):
• c). cyclizing the compound of formula (4) to form a compound of formula (5):
• and
• d). converting compound (5) to 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one (1) (Perampanel). 29 (New):
• The process according to claim 28, wherein X is selected from the group consisting of halogen, acetal, —C(═O)H, —C(═N)—OH, —C(═O)NH2, sulfonyloxy, NHZ1 wherein Z is H or a nitrogen protecting group, and OZ2 wherein Z2 is a H or a hydroxy protecting group.

The process according to claim 28, wherein Y is OR2 and the process comprises the steps of:

• a). reacting a compound of formula (2) with a formylating agent selected from the group consisting of an alkyl formate and a trialkyl orthoformate to form a compound of formula (6):
• b). reacting compound (6) with aniline to form a compound of formula (7):
• c). cyclizing the compound of formula (7) to a compound of formula (5)
• and
• d). converting of compound (5) to Perampanel (1). 34 (New):
• The process according to claim 33, wherein the formylating agent in step (a) is a trialkyl orthoformate, and compound (2) is converted directly to compound (6).