A volatile organic solvent-free deep eutectic solvent (DES) was prepared by utilizing 1 : 10 ratio of potassium carbonate (PC) as a hydrogen bond acceptor (HBA) and ethylene glycol (EG) as a hydrogen bond donor (HBD). Subsequently, DES was utilized as a solvent in the Pd-catalyzed Suzuki-Miyaura or Sonogashira cross-coupling reactions of boronic acids or acetylenes respectively with in situ generated 2-bromobenzo[2,3][1,4]oxazepino[7,6-b]quinoline, 3 The anhydrous conditions without air exclusion, low catalyst loading, low toxicity, high efficiency, low cost, and bioavailability are the advantages of DES in C−C bond forming reactions. Moreover, a gram-scale reaction under mild conditions with an excellent yield was productive. The one-pot reaction of 6-bromo-2-chloroquinoline-3-carbaldehyde, 1 through 2-bromobenzo [2,3][1,4]oxazepino [7,6-b]quinoline, 3 intermediate, and subsequent Suzuki-Miyaura or Sonogashira coupling was successfully attempted. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim