Patent ID: 6562965
Filing Date: 2003-05-13
Classification: C07C,C07D,Y10S

Abstract:
A process for the preparation of a compound of formula (I): or a pharmaceutically acceptable salt form thereof; wherein:r is an integer from 0 to 4; R1 is independently selected at each occurrence from the group consisting of: H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, â€”NR1cR1d, â€”OR1e, and â€”SR1e; R1c and R1d are independently selected at each occurrence from the group consisting of: H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl; or R1c and ad R1d when taken tog ether form a heterocyclic ring selected from the group consisting of: piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine and thiomorpholine, each heterocyclic ring unsubstituted or substituted with 1-3 C1-C4 alkyl groups; R1e is independently selected at each occurrence from the group consisting of: H, C1-C10 alkyl, C3-C6 cycloalkyl, and C4-C6 cycloalkylalkyl; R2 is selected from the group consisting of: H, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkyl, and C1-C4 alkyl substituted with 0-5 R2a; R2a is independently selected at each occurrence from the group consisting of: H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, halo, CN, C1-C4 haloalkyl, â€”OR2e, and â€”SR2e; and R2e is independently selected at each occurrence from the group consisting of: H, C1-C10 alkyl, C3-C6 cycloalkyl, and C4-C6 cycloalkylalkyl; the process comprising the steps of:(1) reacting a compound of formula (II): â€ƒwith a halogenating agent to form a compound of formula (III): â€ƒwherein X is a halogen derived from the halogenating agent; (2) reacting the compound of formula(III) with a strong base followed by addition of an alkylborate to form a compound of formula (IV): (3) reacting the compound of formula (IV) with a compound of formula (V): â€ƒwherein Y is a second halogen; in the presence of a catalyst and a weak base to form a compound of formula (VI): (4) reacting the compound of formula (VI) with an isomerization base to form a compound of formula (I), or a pharmaceutically acceptable salt form thereof; wherein the compound of formula (V) is prepared by reacting a compound of formula (VII): with a second halogenating agent to give a compound of formula (V).