Processes for the preparation of 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2h)-yl)-n,4-dimethylbenzamide

A process for the preparation of a compound of Formula I:

• comprising the steps:
• a) contacting a compound of formula V:
• with a halogenating reagent in the presence of at least one solvent to produce a compound of Formula IV:
• b) contacting a compound of Formula IV with an hydrolase in the presence of a buffer solution to produce a compound of Formula X:
• c) contacting a compound of Formula X with a activating reagent in the presence of at least one solvent and then contacting the resulting mixture with an amine to produce a compound of Formula IX:
• d) contacting a compound of Formula IX with a substituted benzylhalide in the presence of a base and at least one solvent to produce a compound of Formula I;
• wherein
• X1, X2, X3, X4, X5 and X6 are independently H, halo, or a C1-C6 alkyl;
• R1 is a C1-C6 alkyl or aryl;
• R2 is H, halo, or a C1-C6 alkyl;
• R3 is halo, or a C1-C6 alkyl;
• and
• R4 is H or a C1-C6 alkyl;
• R5 is H, a C1-C6 alkyl or aryl;
• or
• R4, R5, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, hydroxy, hydroxy C1-C4 alkyl, C1-C4 dihydroxyalkyl, or halogen.

A process for the preparation of a compound of Formula I having the following structure:

• comprising the steps:
• a) contacting a compound of formula V having the following structure:
• with 1,3-dibromo-5,5-dimethylhydantoin in the presence of acetonitrile to produce a compound of Formula IV having the following structure:
• b) contacting a compound of Formula IV with Bacillus sp. protease in the presence of a potassium phosphate buffer solution to produce a compound of Formula X having the following structure:
• c) contacting a compound of Formula X with 1,1′-carbonyldiimidazole in the presence of dimethylformamide and then the resulting mixture is contacted with NH2CH3 in tetrahydrofuran to produce a compound of Formula IX having the following structure:
• d) contacting a compound of Formula IX with a compound having the following structure:
• in the presence of potassium carbonate and N-methylpyrrolidinone.