N-methyl-N-phenyl-hydrazine → 5-(Tetrahydro-pyran-4-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid N'-methyl-N'-phenyl-hydrazide

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Reaction Steps

In a 10 mL two-necked flask, the above prepared 5-(tetrahydro-pyran-4-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (50 mg, 164 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.0 mL) and DMF (1 mL) to give a colorless solution. TBTU (78.9 mg, 246 μmol, Eq: 1.5) and N,N-diisopropylethylamine (106 mg, 143 μl, 819 μmol, Eq: 5) were added and the reaction mixture stirred for 10 min at rt before 1-methyl-1-phenylhydrazine (24.0 mg, 23.1 μl, 197 μmol, Eq: 1.2, CAN 618-40-6) was added and the reaction mixture kept overnight at rt. Work up: The reaction mixture was 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 sol., the combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered eventually 62 mg of the title compound as white foam; MS (EI) 410.2 (M+H)+.

Provenance & Evidence