Patent ID: 8642809

Claim:
A method for the synthesis of a compound of the following formula or a pharmaceutically acceptable salt thereof: wherein: -A is independently -A 1 , -A 2 , -A 3 , or -A 4 ; -A 1 is independently C 6-10 carboaryl, and is optionally substituted; -A 2 is independently C 5-10 heteroaryl, and is optionally substituted; -A 3 is independently C 5-7 cycloalkyl, and is optionally substituted; -A 4 is independently C 5-7 heterocyclic, and is optionally substituted; -Q 1 - is independently a covalent bond or —R A —; —R A - is independently —R A1 — or —R A2 —; —R A1 — is independently aliphatic C 2-6 alkylene, and is optionally substituted; —R A2 — is independently aliphatic C 2-6 alkenylene, and is optionally substituted; —R N is independently —H, saturated aliphatic C 1-4 -alkyl, phenyl, or benzyl; and —R B — is independently —R B1 — or —R B2 —; —R B1 — is independently aliphatic C 2-6 alkenylene, and is optionally substituted; —R B2 — is independently aliphatic C 2-6 alkynyl-alkenylene, and is optionally substituted; said method comprising, in order: (a) an alkenyl-acid addition (AAA) step comprising either (i): in order: reacting a compound of Formula (C): with a compound of Formula (D): to form a compound of Formula (E): an optional purification (PUR E ) step comprising optionally purifying said compound of formula (E); and forming a compound of formula (F): either: (i) by a carboxylic acid deprotection (CAD-1) step comprising reacting said compound of Formula (E): with a de-esterification agent, wherein the de-esterification agent is an acid, or an inorganic base, wherein: —X 2 is independently —Cl, —Br, or —I; and —R E is a carboxylic acid-protecting ester group; or (ii): by an alkenyl-carboxylic acid addition (ACAA-1) step comprising reacting a compound of Formula (C): with a compound of Formula (D′): wherein: —X 2 is independently —Cl, —Br, or —I; (b) an optional purification (PUR F ) step comprising optionally purifying said compound of formula (F); (c) forming a compound of formula G by a hydroxamic acid formation (HAF) step comprising: (i) reacting said compound of Formula (F): with either thionyl chloride (SOCl 2 ) or oxalyl chloride (C 2 O 2 Cl 2 ) to form an intermediate product (F′); and (ii) reacting said intermediate product (F′) with hydroxylamine (NH 2 OH) to form a compound of Formula (G): (d) an optional purification (PUR G ) step comprising optionally purifying said compound of formula (G).