The synthesis strategy for new heteroaryl derivatives of suvorexant and JH112 was based on our previously published work . Our envisaged series of fluorinesubstituted heteroaryl derivatives 1a-f contained derivatives of suvorexant with alkylunsubstituted diazepane moiety and various heteroarenes (Figure Starting from 5-fluorobenzoxazole , copper-catalyzed oxidative coupling with either commercially available tert-butyl 1,4-diazepane-1-carboxylate or the (S,S)-secbutyl substituted homopiperazine building block 6, synthesized as previously published , provided compounds 7a and 7b (Scheme 1A). Cleavage of the Boc protection group under acidic conditions gave the secondary amines 8a and 8b, which were coupled to commercially available 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid under standard amide coupling conditions. The final compounds 1a and 1e were obtained after purification by preparative HPLC (Scheme 1A). Scheme 2 shows the syntheses of suvorexant analogs 1b-d bearing the alkylunsubstituted diazepane, to complete the series of target compounds 1a-f (cf. Figure ). Compared to Scheme 1, the order of reaction steps was changed allowing simplified protocols for the straightforward introduction of different heteroaryl scaffolds (Scheme 2). Amide coupling of commercially available tert-butyl 1,4diazepane-1-carboxylate with 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid in the first reaction step was followed by nucleophilic substitution on the respective heteroaryl compounds. The course of the syntheses shown in Scheme 2 used the same reaction types as documented in Scheme 1, providing compounds 1b-d with the variation of the heteroarenes benzooxazole, benzothiazole and quinoxaline. Thus, the series of new OXR ligands 1a-f was successfully synthesised in purities of >98% (HPLC). In addition, the BPin esters 3a, 3c and 3c were successfully obtained as well as the boroxines 4c and 4f, which were selected as labeling precursors for Cu-mediated aromatic 18