[EN] 2-ARYL- AND 2-HETEROARYL-SUBSTITUTED 2-PYRIDAZIN-3(2H)-ONE COMPOUNDS AS INHIBITORS OF FGFR TYROSINE KINASES<br/>[FR] COMPOSÉS DE 2-PYRIDAZIN-3(2H)-ONE À SUBSTITUTION 2-ARYLE ET 2-HÉTÉROARYLE UTILISÉS EN TANT QU'INHIBITEURS DE FGFR TYROSINE KINASES
申请人:ARRAY BIOPHARMA INC
公开号:WO2017070708A1
公开(公告)日:2017-04-27
Provided herein are compounds of the general Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which X, R1, R2, R3, Ring A and z have the meanings given in the specification, which are inhibitors of FGFR1, FGFR2, FGFR3 and/or FGFR4 and are useful in the treatment and prevention of diseases which can be treated with an FGFR inhibitor, including diseases or disorders mediated by FGFR1, FGFR2, FGFR3 and/or FGFR4.
L-Proline was identified as an effective additive to promote the Rosenmund-vonBraun reaction at a lower temperature (80-120 °C). This modified Rosenmund-vonBraun cyanation of aryl bromides exhibits excellent functional-group compatibility, and provide an efficient and convenient approach for the synthesis of aryl nitriles.
4,6-Dibromoresorcinol dimethyl ether was selectively metalated at C-5 with lithium tetramethylpiperidide (LiTMP). A rationale for the selective metalation is proposed.