This compound can be obtained by two related ways: 1) The nitration of minocycline (I) by means of NaNO3 and H2SO4 gives the 9-nitro derivative (II), which is hydrogenated with H2 over Pd/C in 2-methoxyethanol to yield the 9-amino derivative (III). Finally, this compound is acylated with sarcosyl chloride (IV) by means of Na2CO3 in acetonitrile/dimethylpropylenurea. 2) The acylation of the 9-amino derivative (III) with N-(succinimidyloxycarbonyl)carbamic acid tert-butyl ester (V) by means of sodium acetate in THF gives the 9-(tert-butoxycarbonyl)glycylamino substituted compound (VI), which is deprotected with trifluoroacetic acid to afford the 9-glycylamino compound (VII). Finally, this compound is methylated with formaldehyde and simultaneous hydrogenation with H2 over Pd/C in 2-methoxyethanol.
By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II), which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III). Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V). Finally, this compound is treated with tert-butylamine (VI) to yield, after purification, GAR-936.