Oxazole derivatives of tetracyclines

A compound of the formula

• or a pharmaceutically acceptable salt thereof
• wherein:
• X is selected from hydrogen, amino, NR11R12, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, vinyl, optionally substituted, alkynyl of 2 to 12 carbon atoms optionally substituted and halogen:
• R1 and R2 are each independently H or alkyl of 1 to 12 carbon atoms or
• R1 and R2 when optionally taken together with the nitrogen atom to which each is attached form a 3 to 7 membered saturated hydrocarbon ring;
• R11 and R12 are each independently H or alkyl of 1 to 12 carbon atoms or
• R11 and R12 when optionally taken together with the nitrogen atom to which each is attached form a 3 to 7 membered saturated hydrocarbon ring;
• Y is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, alkenyl of 2 to 12 carbon atoms optionally substituted vinyl, alkynyl of 2 to 12 carbon atoms optionally substituted and halogen;
• produced by the process comprising the steps:
• a. reacting 7-(substituted)-8-(substituted)-9-amino-6-demethyl-6-deoxytetracycline of the formula
• or a pharmaceutically acceptable salt thereof
• with 2-chlorotrimethoxyethane in an aprotic solvent to afford a chloro compound of the formula
• b. reacting the chloro compound with an amine R1R2NH to form a substituted amine of the formula
• c. hydrolyzing the substituted amine with acid to give a compound of the formula
• d. isolating the compound or a pharmaceutically acceptable salt thereof.

A compound of the formula

• wherein:
• X is selected from hydrogen, amino, NR11R12, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, vinyl optionally substituted, alkynyl of 2 to 12 carbon atoms optionally substituted and halogen;
• R1 and R2 are each independently H or alkyl of 1 to 12 carbon atoms or
• R1 and R2 when optionally taken together with the nitrogen atom to which each is attached form a 3 to 7 membered saturated hydrocarbon ring;
• R11 and R12 are each independently H or alkyl of 1 to 12 carbon atoms or
• R11 and R12 when optionally taken together with the nitrogen atom to which each is attached form a 3 to 7 membered saturated hydrocarbon ring;
• Y is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, alkenyl of 2 to 12 carbon atoms optionally substituted, vinyl, alkynyl of 2 to 12 carbon atoms optionally substituted and halogen;
• or a pharmaceutically acceptable salt thereof
• produced by the process comprising the steps:
• a. reacting 7-(substituted)-8-(substituted)-9-amino-6-demethyl-6-deoxytetracycline of the formula
• or a pharmaceutically acceptable salt thereof
• with 2-chlorotrimethoxyethane in an aprotic solvent to afford a chloro compound of the formula
• b. reacting the chloro compound with acid to give 9-(2-chloromethylcarbonylamino)substituted-6-demethyl-6-deoxytetracycline of the formula
• c. reacting the 9-(2-chloromethylcarbonylamino)substituted-6-demethyl-6-deoxytetracycline with amine R1R2NH to give a compound of the formula
• d. isolating the compound or a pharmaceutically acceptable salt thereof.