Water → 6-[5-(1-methoxy-1-methyl-ethyl)-3-pyridyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a sealed tube which contained 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 3-bromo-5-(1-methoxy-1-methyl-ethyl)-pyridine (216 mg, 0.937 mmol), Na2CO3 (166 mg, 1.56 mmol) and water (0.5 mL). The mixture is bubbled with Ar for 5 min. Then PdCl2(DPPF) (57 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. for 1 h and then is cooled to room temperature. The reaction mixture is filtered through diatomaceous earth and washed with DCM. The filtration 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 (MeOH/DCM 0 to 5% gradient, then 5%) and then separated 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 resulting material is further purified by C-18 HPLC (31% CH3CN in 2.5 mM NH4HCO3 aqueous solution, isocratic for 15 min plus 5 min wash at 17 ml/min) to obtain 66 mg of the title compound.

Provenance & Evidence