A mixture of 3-(4-bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (209 mg, 0.53 mmol), copper (1) iodide (5 mg, 0.026 mmol), sodium iodide (159 mg, 1.06 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 g, 0.053 mmol) in 1,4-dioxane (1.0 ml) was heated at 105° C. for 24 hours under an argon atmosphere. Copper (1) iodide (5 mg, 0.026 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 μl, 0.053 mmol) were added and heating continued for a further 24 h. Once the reaction was cooled to room temperature, the mixture was partitioned between ethyl acetate (30 ml) and 10% v/v 0.880 ammonia/water (20 ml). The layers were separated and the aqueous phase was extracted with DCM (30 ml). The combined organic layer was dried over sodium sulphate, filtered and evaporated then the residue was purified by flash chromatography a Si-SPE (eluting with pentane:diethyl ether, gradient 90:10 to 70:30) to afford the title compound as a yellow solid (174 mg, 74%). LCMS (method B): RT=3.97 min, M+H+=443.
