Yield:952182-50-2 100%

Reaction Conditions:

with oxalyl dichloride;N,N-dimethyl-formamide in dichloromethane at 0 - 20; for 1 h;

Steps:

1-(4-Bromo-benzyl)-5-methyl-1 H-[1 ,2,3]triazole-4-carboxylic acid [5-chloro-2-(1 H- tetrazol-5-yl)-phenyl]-amide (3)To a stirred suspension of the commercial 1 -(4-bromo-benzyl)-5-methyl-1 H- [1 ,2,3]triazole-4-carboxylic acid (0.200 g, 1 eq) in DCM (15 ml), an excess of oxalyl chloride (1 ml) is added drop wise at 0⁰C, followed by 1 -2 drops of dry DMF. The resulting yellow solution is allowed to reach room temperature spontaneously and then stirred at room temperature until starting material disappears completely on TLC (~1 hour). The mixture is then evaporated to dryness under vacuum and the residue is taken up in DCM and washed with cold aqueous NaHCO₃. The organic phase, dried over MgSO₄ and evaporated to dryness, gives 0.212 g (-100% yield) of 1 -(4-bromo- benzyl)-5-methyl-1 H-[1 ,2,3]triazole-4-carbonyl chloride, which is dissolved in TOL (10 ml) and Py (0.5 ml) under nitrogen. The new solution is ice-cooled and 5-chloro-2-(1 H- tetrazol-5-yl)-phenylamine (0.119 g, 0.9 eq) (prepared as described by Valgeirsson et a/, in Journal of Medicinal Chemistry 2004 47 (27) 6948-6957) is added and stirring is continued under nitrogen at room temperature overnight. The reaction mixture is evaporated to dryness and the crude solid residue is purified by crystallisation from MeOH (0.105 g, 22% yield). LC-ESI-HRMS of [M-H]- shows 471.007 Da. CaIc. 471.008423 Da, dev. -3 ppm.

References:

WO2008/138917,2008,A1 Location in patent:Page/Page column 25-26