Cross-linked glycopeptide-cephalosporin antibiotics
View Patent ↗This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.
1. A process for preparing a compound of the formula:
or a salt thereof; the process comprising:
(a) contacting vancomycin or a salt thereof with a coupling reagent; and
(b) contacting the reaction mixture from step (a) with a compound of the formula:
or a salt thereof.
2. The process of claim 1 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxybenzotriazole.
3. The process of claim 1 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxy-7-azabenzotriazole.
4. The process of claim 1 , wherein the coupling reagent comprises O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.
5. The process of claim 1 , wherein the process is conducted in a diluent comprising N,N-dimethylformamide, dimethyl sulfoxide, or a combination thereof.
6. The process of claim 1 , wherein step (a) of the process is conducted in the presence of diisopropylethylamine.
7. The process of claim 1 , wherein step (b) of the process is conducted in the presence of 2,4,6-collidine.
8. The process of claim 1 , wherein a vancomycin hydrochloride salt is employed in step (a).
9. A process for preparing a compound of the formula:
or a salt thereof; the process comprising reacting a compound of the formula:
or a salt thereof, with a reaction mixture formed by contacting vancomycin or a salt thereof with a coupling reagent.
10. The process of claim 9 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxybenzotriazole.
11. The process of claim 9 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxy-7-azabenzotriazole.
12. The process of claim 9 , wherein the coupling reagent comprises O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.
13. The process of claim 9 , wherein the process is conducted in a diluent comprising N,N-dimethylformamide, dimethyl sulfoxide, or a combination thereof.
14. The process of claim 9 , wherein the process is conducted in the presence of 2,4,6-collidine.
15. A process for preparing a compound of the formula:
or a salt thereof; the process comprising:
(a) contacting vancomycin hydrochloride with a coupling reagent in the presence of diisopropylethylamine; and
(b) contacting the reaction mixture from step (a) with a compound of the formula:
or a salt thereof, in the presence of 2,4,6-collidine.
16. The process of claim 15 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxybenzotriazole.
17. The process of claim 15 , wherein the coupling reagent comprises benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 1-hydroxy-7-azabenzotriazole.
18. The process of claim 15 , wherein the coupling reagent comprises O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.