Methods for Synthesizing and Purifying Aminoalkyl Tetracycline Compounds

A method for the synthesis of an aminoalkyl tetracycline compound, comprising:

• contacting a tetracycline compound with a N-hydroxymethyl-phthalimide in the presence of a water scavenger and an acid under appropriate conditions to form an aminomethyl tetracycline intermediate compound;
• treating said aminomethyl tetracycline intermediate compound with methylamine under second appropriate conditions to form a second aminomethyl tetracycline intermediate;
• treating said second aminomethyl tetracycline intermediate under appropriate hydrogenation conditions, such that an aminomethyltetracycline compound is formed.

A method of purifying alkylaminomethyl minocycline compounds, comprising:

• injecting an aqueous low pH solution of said compound into an HPLC in a polar organic solvent gradient, and combining the product fractions, such that the alkylaminomethyl minocycline compound is purified.

The method of claim 45, wherein a base is added to said aqueous layer such that the pH is between about 7.5 and 8.5 to form a neutral solution.

A method of removing hydrophobic impurities and oxidative degradents from an alkylaminomethyl minocycline compound, comprising dissolving said minocycline compounds in an aqueous solution of a pH of 4.0-4.5, washing said aqueous solution with a non-polar organic solvent, and discarding said non-polar organic solvent and retaining said aqueous solution, such that hydrophobic impurities and oxidative degradents are removed from said alkylaminomethyl minocycline compound.

A method of removing β epimer and by products from an alkylaminomethyl minocycline compound, comprising dissolving said minocycline compounds in an aqueous solution of a pH of 7.5-8.5, washing said aqueous solution with a non-polar organic solvent, and discarding said aqueous solution and retaining said non-polar organic solution, such that β epimer and by products are removed from said alkylaminomethyl minocycline compound.