•Novel Pd-Catalysed 3-methyl Indole based Analogues were synthesised via Suzuki-Miyaura and Buchwald Hartwig coupling.•The synthesized compounds were evaluated in vitro for human pancreatic cancer cell inhibition assay on Mia PaCa-2 cell line.•The molecular docking studies on HIF-1α and in silico ADMET studies were performed.•Compound 9d exhibited better cytotoxic effect in the series and could be considered as lead for development as a cytotoxic active compound. Indole is a most prerogative moiety in the evaluation of anticancer agents for its versatility and bio-diversity. The indole based compounds have been reported by the researchers in the last decade with potent anticancer activities. The coupled indole ring system with other biodynamic moieties is known to increase the bio-efficiency. Hence, a series of 3-methyl-indole-2-pyrindine coupled secondary amines have been synthesized via Suzuki-Miyaura and Buchwald Hartwig coupling. The compounds 9a-e have been docked against Hypoxia-inducible factor 1α (HIF-1α) enzyme to demonstrate the binding interactions with the active site, shown the binding affinity from -7.5 to -8.1 Kcal/mol and disclosed the potentiality of synthesized compounds to bind and inhibits the HIF-1α (Pdb Id: 3KCX) pathway and predicted several in silico ADMET descriptors for the 3-methyl Indole analogues. The molecules were screened for their anti-pancreatic cancer activity and tested against Mia PaCa-2 cell line by MTT assay, revealed that; compound 9d exhibited a greater antiproliferation activity in the series, with IC50 of 73.63±2.05 µM. Our present findings revealed that 9d might be a pursuable lead for further anti-pancreatic cancer studies. Display omitted