In a sealed tube which contains the crude 6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (generated according to the procedure for Step 3 of Example 16 in 5 ml 1,4-dioxane, 0.78 mmol) is added 2-(5-bromo-pyridin-3-yl)-1,1,1-trifluoro-propan-2-ol (253 mg, 0.94 mmol.), Na2CO3 (166 mg, 1.56 mmol) and water (1.0 ml). The mixture is bubbled with Ar for 5 min. Then PdCl2(DPPF) DCM complex (64 mg, 0.078 mmol) is added. The mixture is then bubbled with Ar for 5 min. The cap is sealed and the mixture is heated at 90° C. in oil bath for 1 h and then is cooled to room temperature. The reaction mixture is filtered through diatomaceous earth and washed with DCM. The filtrate is partitioned between water and DCM. The aqueous phase is extracted with DCM. The combined DCM phases are concentrated. The crude is separated by flash silica gel column (EtOAc/heptane 0 to 100% gradient, then 100%). The fractions which contain the desired product are combined, concentrated and further purified by C-18 prep HPLC (MeCN with 0.1% TFA/Water with 0.1% TFA, 20 ml/min, 0 to 65% gradient over 10 min run). The desired fractions are combined and basified by 1N Na2CO3 to pH=10, and is extracted by DCM. The DCM phases are combined and concentrated under vacuum to obtain 69 mg of the title compound.
