Process for making a 4-amino-4-oxobutanoyl peptide cyclic analogue, an inhibitor of viral replication, and intermediates thereof

A process of preparing a compound ACH-0142684 represented by the structure:

• or its pharmaceutically acceptable salt, comprising
• reacting nonenoic acid (19) with 4-benzyl-2-oxazolidinone to obtain a compound (20);
• wherein the compound (20) is then reacted a strong base and t-butyl haloacetate to obtain a compound (21);
• followed by reacting the compound (21) with hydrogen peroxide in the presence of a base such as LiOH to provide Compound C;
• reacting a compound (29) with the Compound C to obtain a compound (30)
• wherein the Compound C is reacted in the presence of a catalyst to join and merge the vinyl groups with the expulsion of ethylene,
• the t-butyl ester group is converted to a carboxylic acid group;
• and
• the carboxylic acid group is reacted with 3,3-difluoropiperidine;
• thereby forming the compound ACH-0142684.

An intermediate compound of the formula:

• wherein
• R1 is hydroxyl, C1-C6 alkoxy, aryloxy, benzyloxy, 4-methoxybenzyloxy, C1-C6 acyloxy, halogen, or N-linked 3,3-difluoropiperidinyl;
• R2 is hydroxyl, N-linked cyclopropylsulfonamide, or N-linked benzenesulfonamide in which the benzene ring is further substituted with 0-2 nitro groups;
• and
• R3 is hydrogen and R4 is halogen, hydroxyl, an O-linked mesylate group, or an O-linked benzenesulfonate group in which the benzene ring is further substituted with 0-1 groups independently chosen from C1-C6 alkyl, C1-C6alkoxy, halogen, and nitro;
• or
• R4 is hydrogen and R3 is hydroxyl or the heterocyclic group