Macrolide synthesis process and solid-state forms

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 R1, R2, and R3:
• R1and R3 are each methyl, and R2 is hydrogen,
• R1and R3 are each hydrogen, and R2 is methyl, or
• R1, R2, and R3 are each hydrogen;
• and
• as to R4, R5, and R6:
• R4 and R6 are each methyl, and R5 is hydrogen,
• R4 and R6 are each hydrogen, and R5 is methyl, or
• R4, R5, and R6 are each hydrogen.