2,4-DI-PIPERIDIN-1-YL-PHENYLAMINE synthesis

Yield:436096-88-7 94%

Reaction Conditions:

with hydrogen;5%-palladium/activated carbon in methanol; for 2 h;

Steps:

23.a

Example 23 5-(N-Hydroxycarbamimidoyl)-furan-2-carboxylic acid (2,4-di-piperidin-l-yl-phenyl)- amide a) S-Cyano-furan-l-carboxylic acid (2,4-di-piperidin-l-yl-phenyl)-arnide; To a solution of 2,4-difluoronitrobenzene (2.09 g, 13.1 mmol) in EtOH (10 mL) at ambient temperature was added piperidine (3.35 g, 39.4 mmol) dropwise. The reaction was allowed to stir overnight and concentrated in vacuo. The residue was dissolved in EtOAc (100 mL), washed with water (2 x 100 mL), dried (Na₂SO₄) and concentrated in vacuo. Purification by silica gel column chromatography (10% EtOAc-hexane) afforded 610 mg EPO (16%) of 2,4-dipiperidinylnitrobenzene as an oil. 2,4-dipiperidinylnitrobenzene (273 mg, 0.94 mmol) was then stirred in the presence of 168 mg of 5% Pd-C in 10 niL of MeOH under H₂ for 2 h. The reaction was filtered through Celite and concentrated in vacuo to afford 230 mg of 2,4-dipiperidinylaniinobenzene (94%) as an oil. Using a procedure similar to Example 4, step (c), 2,4-dipiperidinylaminobenzene (100 mg, 0.38 mmol) was allowed to react with 5-cyano-furan-2-carbonyl chloride (73 mg, 0.46 mmol) in the presence of DIEA (145 μL, 0.83 mmol) to afford 90 mg (62%) of the title compound as a yellow solid. Mass spectrum (ESI, m/z): Calcd.for C₂₂H₂₆N₄O₂, 379.2 (M+H), found 379.2.

References:

WO2006/47504,2006,A1 Location in patent:Page/Page column 68-69