METHOD FOR THE PREPARATION OF INTERMEDIATES USEFUL FOR THE SYNTHESIS OF 1,2,4-TRIAZOLO4,3-APYRIDINES

摘要

The present application discloses a method comprising: (A)(i) admixing a methylnicotinate of Formula (I):wherein R3 is Cl, Br, or I, and R4 is alkyl;with 1,3,5-triazine, and a base, under conditions sufficient to form a naphthyridinone of Formula (II):(ii) admixing the naphthyridinone of Formula (II) with methoxyethanol, a base, and a copper (I) catalyst, under conditions sufficient to form 3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one ("NAPH"):or (B):(i) admixing protected 2-alkoxypyridin-4-ylamine with a lithium reagent, under conditions sufficient to form the protected N-(3-formyl-4-amino-2-alkoxy)pyridine:wherein PG is a protecting groupwherein R ⁸ is an alkyl group;(ii) admixing the protected N-(3-formyl-4-amino-2-alkoxy)pyridine with 1-hydroxy-2-(2-methoxyethoxy)ethane-1 -sulfonate:and base, under conditions sufficient to form a naphthyridine of Formula (III):; and(iii) acidifying the naphthyridine of Formula (III), under conditions sufficient to form 3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one ("NAPH"):