Diisopropylethylamine → 5-Cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid N'-(4-fluoro-phenyl)-N'-methyl-hydrazide

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Reaction Steps

In a 10 mL two-necked flask, the above synthesized 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinic acid (50 mg, 191 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.00 ml) and DMF (1 ml) to give a colorless solution. TBTU (92.2 mg, 287 μmol, Eq: 1.5) and N,N-diisopropylethylamine (124 mg, 167 μl, 957 μmol, Eq: 5) were added and the reaction mixture was stirred for 10 min at rt; then 1-(4-fluorophenyl)-1-methylhydrazine hydrochloride (40.6 mg, 230 μmol, Eq: 1.2; CAN 1978-54-7) was added and the reaction allowed to proceed over night at rt. The reaction mixture was then quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl solution. The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered finally 70 mg of the title product as white semisolid; MS (EI) 384.3 (M+H)+.

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