Quinazoline ditosylate salt compounds

• Main Authors: ROSCHANGAR, FRANK, MCCLURE, MICHAEL SCOTT, OSTERHOUT, MARTIN HOWARD, SACCHETTI, MARK JOSEPH
• Format: Patent
• Language: English
• Published: 29.09.2006
• Edition: 7

Quinazoline compounds, anhydrate and hydrate ditosylate salts thereof, as well as use and preparation of the same are disclosed. Particularly disclosed are ditosylate salts of 4-quinazolineamines. These compounds are inhibitors of various protein tyrosine kinases (PTKs) of the erbB family and consequently are useful in the treatment of disorders mediated by aberrant activity of such kinases. Particularly disclosed is a process for preparing a compound of formula (C), which comprises the steps of: reacting a compound of formula (A) with a compound of formula (B) to form the compound of formula (C), wherein U is a phenyl group substituted by an R2 group and by at least one independently selected R4 group, where R2 is in the para- position relative to the bond from U to the linking NH group and represents benzyloxy, fluorobenzyloxy, benzyl, phenoxy or benzenesulphonyl and the R4 group is selected from halo or C1-4 alkoxy; and the compound of formula (A) is generated in situ, and L is iodine or bromine; R is -C(Q)(T)W where Q and T are independently selected from -OCH3 or -OCH2CH3 and W is hydrogen; and Z is B(OH)2; or the compound of formula (A) is generated in situ, and L is iodine or bromine; R is -C(O)H, and Z is B(OH)2; or the compound of formula (B) is generated in situ and L is B(OH)2; R is -C(O)H; and Z is bromine; or the compound of formula (B) is reacted with the compound of formula (A) regioselectively, where neither of the compounds of formula (A) or (B) is generated in situ, and L is iodine or bromine; R is -C(O)H; and Z is hydrogen.