Adam W. Sledeski

A convergent synthesis of an LTD4 antagonist, RG12525

Abstract An efficient, convergent synthesis of an LTD 4 antagonist, RG12525 ( 1 ) has been achieved through the alkylation of the (2-quinolinylmethoxy)phenol ( 2 ) with either a triphenylmethyl protected tetrazole synthon ( 4a ) or with a tetrahydropyranyl derivative ( 4b ). Preparation of synthons 4a and 4b , as well as novel preparation of 2 is described.

Approaches to p-hydroxyphenoxymethylquinolines which avoid intermediate chloromethylquinolines for the synthesis of the LTD4 antagonist, RG 12525

As part of an effort to develop an industrial synthesis of the LTD4 antagonist RG 12525 (1), several approaches to the intermediate (2-quinolinylmethoxy)phenol 3 were investigated that avoided the generation of the lachrymatory sensitizer α-chloro-2-methylquinoline 2. Utilization of a cyclic sulfate in place of α,α′-dichloro-o-xylene 4 showed promise as a selective dialkylating agent in the conversion of 3 to RG 12525 (1).