Patent ID: 8889855

Claim:
A method of preparing a compound of Formula I or a salt thereof: comprising contacting a compound of Formula I-A: with a carboxylic acid of the formula R—COOH in the presence of a coupling reagent, a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base to form the compound of Formula I, or a salt thereof; wherein X is hydrogen or halo; Y is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and —C(═O)R 5 ; R 1 is selected from the group consisting of hydrogen, — and —OR 17 ; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is methyl, —CH 2 OH, or —CH 2 OR 17 ; R 4 is —OH, —OR 17 or —SH; R 5 is C 1 -C 6 alkyl or benzyl; R 17 is a hydroxy protecting group; R is selected from the group consisting of alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclic, wherein the alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocyclic is optionally substituted with one to three R 10 , or is L is selected from optionally substituted C 1 -C 20 alkylene, C 3 -C 8 cycloalkylene, and optionally substituted C 1 -C 20 alkylene wherein one or more of the —CH 2 — group is independently replaced with C 3 -C 8 cycloalkylene, —O—, —S—, —C(O)—, —NR 8 —, —C(═O)NR 8 —, —NR 8 C(═O)—, —SO 2 NR 8 —, or —NR 8 SO 2 —; substituted C 1 -C 20 alkylene is C 1 -C 20 alkylene substituted with 1 to 4 —SO 3 H, —P(O)(OH) 2 or R 23 , wherein each R 23 is independently C 1-6 alkyl optionally substituted with 1 or 2 substituents independently selected from the group consisting of SH, S—C 1-4 alkyl, —CONR 11 R 11 , and —NR 11 Pr; R 7 is hydrogen, C 1 -C 6 alkyl or an amino acid side chain; R 8 is hydrogen or C 1-6 alkyl; each R 10 is independently selected from the group consisting of —NR 11 Pr, —NR 11 COCH 2 Br, —COOR 12 , —CONR 11 R 11 , —NR 11 COR 13 , —S—S—R 13 , —Si(R 13 ) 3 , alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclic; each R 11 is independently hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclic, or the two R 11 together with the nitrogen form a heterocyclic, wherein the heterocyclic is optionally substituted with one or two oxo; Pr is an amino protecting group; R 12 is C 1 -C 6 alkyl, or benzyl; and each R 13 is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl, and heterocyclic.