Process for preparing 2-(4-pyridyl)amino-6-dialkyloxyphenyl-pyrido[2,3-d]pyrimidin-7-ones

A process for preparing a compound of the formula

• 22
• comprising reacting 4-aminopyridine with a compound of the formula
• 23
• in the presence of a base.

A compound of the Formula I

• 24
• wherein:
• Ar is phenyl, substituted phenyl, or heteroaromatic;
• R′ and R″ independently are hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or phenyl;
• and
• R2 is (CH2)nPh, where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• heteroaromatic, cycloalkyl, C1-C6 alkyl and C2-C6 alkenyl, where the alkyl and alkenyl groups may be substituted by NR5R6, phenyl, substituted phenyl, cycloalkyl, and where R5 and R6 are independently C1-C6 alkyl, C2-C6 alkenyl, (CH2)nPh where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• cycloalkyl, heteroaromatic, and R5 and R6 taken together with the nitrogen to which they are attached can complete a ring having 3 to 7 carbon atoms and optionally containing 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, substituted nitrogen, oxygen, and sulfur.

A process for preparing a compound of Formula II

• 25
• wherein:
• Ar is phenyl, substituted phenyl, or heteroaromatic;
• R′ and R″ independently are hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or phenyl;
• and
• R2 is (CH2)nPh, where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• heteroaromatic, cycloalkyl, C1-C6 alkyl, and C2-C6 alkenyl, where the alkyl and alkenyl groups may be substituted by NR5R6, phenyl, substituted phenyl, cycloalkyl, and where R5 and R6 are independently C1-C6 alkyl, C2-C6 alkenyl, (CH2)nPh where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• cycloalkyl, heteroaromatic, and R5 and R6 taken together with the nitrogen to which they are attached can complete a ring having 3 to 7 carbon atoms and optionally containing 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, substituted nitrogen, oxygen, and sulfur
• comprising reacting an aminopyridine of formula
• 26
• with a compound of Formula II
• 27
• in an unreactive organic solvent.

A compound of Formula III

• 28
• wherein:
• Ar is phenyl, substituted phenyl, or heteroaromatic;
• R′ and R″ independently are hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or phenyl;
• and
• R2 is hydrogen, (CH2)nPh, where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• heteroaromatic, cycloalkyl, C1-C6 alkyl, and C2-C6 alkenyl, where the alkyl and alkenyl groups may be substituted by NR5R6, phenyl, substituted phenyl, cycloalkyl, and where R5 and R6 are independently C1-C6 alkyl, C2-C6 alkenyl, (CH2)nPh where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• cycloalkyl, heteroaromatic, and R5 and R6 taken together with the nitrogen to which they are attached can complete a ring having 3 to 7 carbon atoms and optionally containing 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, substituted nitrogen, oxygen, and sulfur.

A process for preparing a 2-alkylsulfanyl pyridopyrimidine of Formula IV

• 29
• wherein:
• Ar is phenyl, substituted phenyl, or heteroaromatic;
• and
• R2 is hydrogen, (CH2)nPh, where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• heteroaromatic, cycloalkyl, C1-C6 alkyl, and C2-C6 alkenyl, where the alkyl and alkenyl groups may be substituted by NR5R6, phenyl, substituted phenyl, cycloalkyl, and where R5 and R6 are independently C1-C6 alkyl, C2-C6 alkenyl, (CH2)nPh where Ph is phenyl or substituted phenyl, and n is 0, 1, 2, or 3;
• cycloalkyl, heteroaromatic, and R5 and R6 taken together with the nitrogen to which they are attached can complete a ring having 3 to 7 carbon atoms and optionally containing 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, substituted nitrogen, oxygen, and sulfur comprising reacting an aryl acetic acid ester of the formula
• 30
• with a 2-alkylsulfanyl-4-alkylamino-pyrimidine-5-carboxaldehyde of the formula
• 31