Propargyl alcohol → 4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

Participants

Reaction Steps

4-(2-Fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide was reacted with propargyl alcohol in the presence of CuI, (Ph3P)2PdCl2 and TEA in THF/DMF (1:1) as for example 2. The residue resulting from removal of the reaction solvents under reduced pressure was purified by column chromatography on silica gel (10% MeOH/CH2Cl2 as eluant) to give 4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a cream solid (89%). 1H NMR [(CD3)2SO, 400 MHz] δ 10.27 (s, 1H), 8.40 (t, J=5.4 Hz, 1H), 8.25 (s, 1H), 7.48 (t, J=8.5 Hz, 1H), 7.39 (dd, J=11.6, 1.8 Hz, 1H), 7.27 (dd, J=8.3, 1.4 Hz, 1H), 5.70 (s, 1H), 5.34 (t, J=6.1 Hz, 1H), 4.47 (t, J=5.1 Hz, 1H), 4.30 (d, J=6.0 Hz, 2H), 3.46 (q, J=5.9 Hz, 2H), 3.38 (s, 3H), 3.27 (q, J=6.5 Hz, 2H), 1.66 (pentet, J=6.7 Hz, 2H). LCMS (APCI+) calcd for C19H21FN3O4 374 (MH+), found 374.

Provenance & Evidence