Patent ID: 8263753

Claim:
A process for making a macrolide or a salt thereof, wherein: the macrolide corresponds in structure to Formula (I): the process comprises: reacting tylosin A or a salt thereof, a piperidinyl compound of Formula (II), and formic acid in the presence of a non-polar solvent to form a 20-piperidinyl-tylosin compound, reacting a 20-piperidinyl-tylosin compound with an acid to form a 23-O-mycinosyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound, reacting a 23-O-mycinosyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound with an acid to form a 23-hydroxyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound, activating a 23-hydroxyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound with an activating agent to form an activated compound, or reacting an activated compound with a piperidinyl compound of Formula (VII); wherein the piperidinyl compound of Formula (II) corresponds in structure to: the 20-piperidinyl-tylosin compound corresponds in structure to Formula (III): the 23-O-mycinosyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound corresponds in structure to Formula (IV): the 23-hydroxyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound corresponds in structure to Formula (V): the activated compound corresponds in structure to Formula (VI): the piperidinyl compound of Formula (VII) corresponds in structure to: L is a leaving group; and as to R 1 , R 2 , and R 3 : R 1 and R 3 are each methyl, and R 2 is hydrogen, R 1 and R 3 are each hydrogen, and R 2 is methyl, or R 1 , R 2 , and R 3 are each hydrogen; and as to R 4 , R 5 , and R 6 : R 4 and R 6 are each methyl, and R 5 is hydrogen, R 4 and R 6 are each hydrogen, and R 5 is methyl, or R 4 , R 5 , and R 6 are each hydrogen.