1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Bipyridinyl-4-carboxylic acid amide

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Reaction Steps

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (3.42 g, 12.6 mmol), 5′-amino-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid amide (which was the product from the catalytic hydrogenation of 5′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid amide: 2.93 g, 12.6 mmol, 200 mL EtOH/THF/EtOAc mixture, 50 psi H2, 7 hr, with 300 mg of Pd/C 10%), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.89 g, 15.1 mmol) and DMAP (catalytic) in anhydrous DMF (25 mL) was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (400 mL) and washed with aqueous ammonium chloride (saturated, 200 mL), sodium bicarbonate (saturated, 200 mL with addition of brine to clear emulsion) and brine (100 mL). The aqueous ammonium chloride was extracted with ethyl acetate (200 mL) which was subsequently washed with brine (100 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and tritrated from boiling ethyl acetate to give 5′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3,4,5,6-tetrahydro-2H-1,2′]bipyridinyl-4-carboxylic acid amide (1.5 g, 26%) as a light brown solid. LCMS calcd for C22H20F3N5O3 (m/e) 459, obsd 460 (M+H).

Provenance & Evidence