A convergent synthetic strategy led us to the target structure 7 (8-azo-cAMP). It allows synthesizing the azobenzene derivative independently of the cAMP precursor. With this, the number of subsequent reaction steps is limited to a maximum of four, which reduces the number of reactions using valuable late-stage intermediates. To connect the photochromic azobenzene moiety to cAMP, a Suzuki-Miyaura C-C cross-coupling reaction was selected as it tolerates aqueous conditions. Furthermore, it has already been used to connect alkyl and aryl moieties to nucleic acids, nucleosides, as well as nucleotides. The boronic acid pinacolato ester 4 and 8-Br-cAMP 6 are the key intermediates coupled in the last step of the synthetic procedure (Scheme 1). To access them, bromination of 1 with N-bromosuccinimide (NBS) in acetonitrile (MeCN) selectively led to the para-brominated 2,6-difluoroaniline 2 in high yield (89%). Over three days, 2 was converted to the para-brominated azobenzene 3 via a Mills coupling with 1,3-difluoro-2-nitrosobenzene in good yield (78%). Literature reports show the bathochromic influence of the tetra-ortho-substitution with fluorine atoms, as well as improved stability against (bio-)degradation, more pronounced geometry changes upon isomerization, and negligible thermal re-isomerization of Z to E. Hence, this substitution pattern was also applied within this work. The bromine substituent of 3 was interconverted efficiently (93% yield) into a boronic acid pinacolato ester substituent by Miyaura-type borylation under inert conditions in 1,4-dioxane. Therefore, Pd(dppf)Cl 2 (dppf = 1,1'-bis(diphenylphosphino)ferrocene) was used as a catalyst in the presence of KOAc at elevated temperatures (110 °C) overnight. Regioselective bromination of compound 5 was accomplished by adding elemental bromine to an aqueous solution of cAMP (5) buffered with NaOAc. After quenching any remaining bromine with Na 2 SO 3 , compound 6 precipitated out and was purified by several washing steps with water, isopropanol ( i PrOH), and diethyl ether (Et 2 O). For further purification, 6 was re-dissolved in water by adding NaHCO 3 . By acidifying the solution with HBr, it precipitated out again in higher purity. Using P(m-C 6 H 4 SO 3 Na) 3 as a water-soluble ligand for palladium, chromophore 4 could be coupled to 6 regioselectively at position 8 via a Suzuki-Miyaura C-C cross-coupling. The reaction was performed in H 2 O/MeCN (2:1) as a solvent mixture.