3,5-Dimethylphenol (I) was alkylated with ethyl 4-bromobutyrate (II) to provide the (dimethylphenoxy)butyrate ester (III), which was hydrolyzed under basic conditions to yield acid (IV). This was sulfonated with chlorosulfonic acid, and the resultant sulfonyl chloride (V) was condensed with Boc-diaminopropanoic acid (VI) to afford sulfonamide (VII). Coupling of (VII) with mono-benzyloxycarbonyl ethylenediamine (VIII) furnished amide (IX). Then, acid cleavage of the Boc protecting group of (IX) provided amine (X).
Amine (X) was coupled with carboxylic acid (XI) to afford the corresponding amide (XII) (1,2). Basic hydrolysis of the ester group of (XII) gave acid (XIII), and subsequent cleavage of the remaining protecting groups of (XIII) with trifluoroacetic acid in the presence of triethylsilane furnished (XIV).
Coupling of the succinimidyl ester of protected glutamic acid (XVI) with glutamic acid gamma-tert-butyl ester (XV) provided the protected dipeptide (XVII), which was then activated with tetrafluorophenol (XVIII) by means of EDC in DMF to yield the tetrafluorophenyl ester (XIX). Condensation of (XIX) with amine (XIV) produced amide (XX), whose N-benzyloxycarbonyl group was then removed by hydrogenolysis over Pd/C to yield amine (XXI).
Acylation of amine (XXI) with tetraazacyclododecanetetraacetic acid tri-tert-butyl ester (XXII) produced amide (XXIII) (1). After acidic cleavage of the tert-butyl ester groups of (XXIII), the resultant macrocyclic tetraamine (XXIV) was complexed with 111InCl3 in the presence of NH4OAc buffer to furnish the title indium-111 complex.
In a related procedure, intermediate (XII) was first deprotected by hydrogenolysis of the N-benzyloxycarbonyl group, yielding amine (XXV). Coupling of this amine with the dipeptide (XVII) furnished adduct (XXVI), which was again deprotected by hydrogenolysis, yielding (XXVII).
Coupling of (XXVII) with the macrocyclic tetraacetic acid tri-tert-butyl ester (XXII) produced amide (XXVIII). Basic hydrolysis of the methyl ester group of (XXVIII), followed by acidic cleavage of the remaining protecting groups, furnished intermediate (XXIV), which was finally complexed as above.