2-Iodobenzoic acid → Methyl 2-((4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)benzoate

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Reaction Steps

Compound Ic-7 can be synthesized by reacting commercially available 3,3′-dimethoxy-[1,1′-biphenyl]-4,4′-diamine (1 equivalent) with 1.2 equivalents of the commercially available methyl ester of iodobenzoic acid in the presence of Pd2(dba)3/DPPP (0.1-0.5 equiv) and 1.2 equivalents Cs2CO3 in toluene at 110° C. for 20 h with vigorous stirring. The intermediate compound methyl 2-((4′-amino-3,3′-dimethoxy-[1,1′-biphenyl]-4-yl)amino)benzoate is isolated by flash chromatography on a C18 column. The product is then reacted by addition of 1.2 equivalent of methyl 2-iodo-5-methylbenzoate in the presence of catalytic (0.1-0.5 equiv) Pd2(dba)3/DPPP and 1.2 equivalents anhydrous, finely powdered Cs2CO3 in toluene at 110° C. for 20 h to yield methyl 2-((3,3′-dimethoxy-4′-((2-(methoxycarbonyl)phenyl)amino)-[1,1′-biphenyl]-4-yl)amino)-5-methylbenzoate. The methyl esters can then be hydrolyzed under basic conditions followed by acidification to yield compound Ic-7,2-((4′-((2-carboxyphenyl)amino)-3,3′-dimethoxy-[1,1′-biphenyl]-4-yl)amino)-5-methylbenzoic acid.

Provenance & Evidence