Patent ID: 8518900

Claim:
A crystalline macrolide or a salt thereof produced by a process, wherein the macrolide corresponds in structure to Formula (I): wherein the process comprises: reacting tylosin A or a salt thereof, a piperidinyl compound of Formula (II), and formic acid in a presence of a non-polar solvent to form a 20-piperidinyl-tylosin compound, reacting the 20-piperidinyl-tylosin compound with an acid to faun a 23-O-mycinosyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound, reacting the 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 the 23-hydroxyl-20-piperidinyl-5-O-mycaminosyl-tylonolide compound with an activating agent to form an activated compound, reacting the activated compound with a piperidinyl compound of Formula (VII) to provide a crude product; and crystallizing the crude product to produce a crystalline macrolide; 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, wherein the crystalline macrolide or salt thereof has a melting point of from about 192 to about 195° C. and at least one of the following characteristics: an FT-Raman spectrum comprising an absorption band at one or more frequencies selected from the group consistint of about 2935, about 1633, about 1596, about 1712, about 1683, and about 781 cm −1 , wherein the FT-Raman spectrum is substantially as shown in FIG. 2 ; a powder X-ray diffraction spectrum comprising at least one peak selected from the group consisting of 5.0 (±0.2) and 5.6 (±0.2) degrees 2Θ, wherein the powder X-ray diffraction spectrum is substantially as shown in FIG. 1 ; or an attenuated total reflection infrared spectrum comprising an absorption band at one or more frequencies selected from the group consisting of about 2932, about 1711, about 1682, about 1635, about 1599, about 1442, about 1404, about 1182, about 1079, about 1053, about 1008, about 985, about 842, and about 783 cm −1 , wherein the attenuated total reflection infrared spectrum is substantially as shown in FIG. 6 .