| Abstrakt: |
A process of preparing a compound of Formula IA: comprising the step of: i) coupling an amide of formula (1'): with a pyrimidine compound of formula (2): in an aprotic organic solvent in the presence of a base, to form, after quenching with an acid, an intermediate of formula (3'): and ii) at a pH>5, optionally in the presence of added N,O-dimethylhydroxylamine or a salt thereof, allowing the mixture to react to form the compound of formula (4'): iiia) condensing the compound of formula (4') with hydrazine to form the compound of formula (24'): iiib) alkylating intermediate of formula (24') with an alkylating agent of formula (23A) to provide the compound of Formula V: iv) de-methylating the compound of Formula V to form an alcohol compound of formula (9'): v) chlorinating the alcohol compound of formula (9') with phosphoryl chloride o form a compound of Formula VI: and vi) reacting an amine of formula (17): with the compound of Formula VIA, optionally in the presence of a base, to yield the compound of Formula IA, wherein X is a leaving group selected from -Br, -I, -Cl, -F, and a sulfonate ester. The process of claim 1, wherein the compound of formula (2) is prepared by a process comprising the steps of: a) reacting dibromopyrimidine compound of formula (5): with a base in methanol or a methoxide salt in an aprotic solvent to form a bromopyrimidine compound of formula (6): b) coupling the bromopyrimidine compound of formula (6) with ethynyltrimethylsilane, in an aprotic organic solvent in the presence of a base and a Pd catalyst, optionally in the presence of a Cu(I) catalyst, to form a compound of formula (7): and c) de-silylating the compound of formula (7) to form the pyrimidine compound of (2). [Extracted from the article] |
