SIMPLE AND CONVENIENT METHOD FOR OBTAINING VABORBACTAM Russian patent published in 2022 - IPC C07F5/02 A61K31/69 A61P31/04 

FIELD: pharmaceutics.

SUBSTANCE: invention relates to a method for producing vaborbactam I. The method includes steps (1)-(6). In step (1), by providing a reaction of a type II compound and a reagent for the introduction of a protective group of the hydroxy group, a type III compound is obtained. In step (2), by providing a reaction of a type III compound with an amine compound, a type IV compound is obtained. In step (3), by providing a reaction of a type IV compound with a borane or borate compound in the presence of a catalyst E and a ligand, a type V compound is obtained, wherein the specified ligand is a combination of benzylamine and triphenylphosphine oxide. In step (4), by conducting a protective group removal reaction against a type V compound, the protective group for the amino group is removed to obtain a type VI compound. In step (5), by providing an amination reaction of a type VI compound with an amination reagent, a type VII compound is obtained, with the specified amination reagent being 2-thiophenacetyl chloride or 2-thiophenacetic acid. In step (6), vaborbactam I is obtained by cyclization and hydrolysis of type VII compounds. In these formulas, R is methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, sec-butyl or tert-butyl; the protective group PG is trimethylsilyl (TMS), tert-butyl-dimethylsilyl (TBDMS), benzyl (Bn), methylsulfonyl (Ms), p-toluenesulfonyl (Ts), trifluoroacetyl (TFA) or acetyl (Ac) ; R₃ is hydroxyl, benzoyl, phenylacetyl, 2-thiophenacetyl or alkyl sulfinyl; n is 0, 1, 2 or 3; if n is 0, then R₁ and R₂ are alkyl groups or aryl groups; if n equals 1, 2 or 3, then R₁ and R₂ are alkyl groups containing from 1 to 4 carbon atoms.

EFFECT: proposed method is safe, simple, convenient, does not require harsh conditions and has a low cost, since the raw material has a reasonable price.

8 cl, 10 ex