3-Bromopyridine → 2-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester

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Reaction Steps

A mixture of 7-bromo-2-(3-ethyl-ureido)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid ethyl ester (8)(240 mg, 0.67 mmol), (Ph3P)2PdCl2 (24 mg, 0.03 mmol) and CuI (13 mg, 0.07 mg) were suspended in dry toluene (5 mL). A solution of 3-pyridyltrimethylstannane [195 mg, 0.81 mmol; prepared from 3-bromopyridine according to the procedure of J. Org. Chem., 64(19), 6999-7008 (1999)] in toluene (5 mL) was added, followed by LiCl (143 mg, 3.37 mmol) as a single portion. The entire mixture was heated at reflux under nitrogen for 2 h. The reaction mixture was allowed to cool, then diluted with 10% MeOH/CH2Cl2 (80 mL). This organic solution was washed with water (80 mL), 1 M KF solution (80 mL) and brine (80 mL). The organic layer was filtered to remove inorganic solids, dried (Na2SO4), and the solvent removed under reduced pressure to give a solid which was purified by chromatography on silica (2% MeOH/CH2Cl2 as eluant). Transesterification from the ethyl to the methyl ester occurred during workup and chromatography. 2-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester was isolated; mp. 211-213° C. LCMS (APCI+) 341. HRMS (FAB+) calcd C16H17N6O3 (MH+) 341.1362, found 341.1358.

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