Diisopropylethylamine → Methyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoate

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Reaction Steps

To a solution of 6-chloro-3-methyl-pyridine-2-carboxylic acid (6.00 g, 0.03508 mol) in CH2Cl2 (50 ml) at 0° C. are added methyl 4-amino-3,5-dimethylbenzoate (5.65 g, 0.03157 mol), and N,N-diisopropylethylamine (15.1 ml, 0.0877 mol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 22.32 g, 0.07016 mol) is added via syringe and stirred at 60° C. After 3 hours, the solvent is removed under reduced pressure and the residue is diluted with water and extracted with ethyl acetate. The organic layers are combined and dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using a gradient of 0-40% ethyl acetate in hexanes to give the title compound as an off-white solid (8.70 g, 74%). Mass spectrum (m/z): 333.2 (M+1).

Provenance & Evidence