3-(3,5-DIFLUOROPHENYL)PICOLINALDEHYDE synthesis

Yield:780801-43-6 61%

Reaction Conditions:

with sodium carbonate;tetrakis(triphenylphosphine) palladium⁽⁰⁾ in tetrahydrofuran;1,2-dimethoxyethane at 90; for 16 h;

Steps:

67 EXAMPLE 67, COMPOUND 67: N1-[3-(3,5-Difluoro-phenyl)-pyridin-2-ylmethyl]-N1-(3,5-dimethyl-pyridin-2-ylmethyl)-butane-1,4-diamine HCl salt

EXAMPLE 67 COMPOUND 67: N¹-[3-(3,5-Difluoro-phenyl)-pyridin-2-ylmethyl]-N¹-(3,5-dimethyl-pyridin-2-ylmethyl)-butane-1,4-diamine HCl salt To a solution of 3-bromo-pyridine-2-carbaldehyde (1.2 g, 6.45 mmol) dissolved in ethylene glycol dimethyl ether (25 mL), THF(10 mL) and saturated solution of Na₂CO₃ (9 mL) was added 3,5 difluorophenyl boronic acid (1.12 g, 7.10 mmol). Purge the mixture with Ar gas (10 min). To this mixture was added Pd(PPh₃)₄ (373 mg, 0.33 mmol) and stir under a positive pressure of Ar at 90° C. for 16 hours. The reaction mixture was quenched with a solution of saturated NaHCO₃ (50 mL). Extract with CH₂Cl₂ (2*50 mL). The combined organic extracts were dried (Na₂SO₄), filtered, and concentrated in vacuo to afford a light yellow oil. Purification via column chromatography on silica gel (CH₂Cl₂:MeOH: 80:20, v/v/v) afforded 3-(3,5-difluoro-phenyl)-pyridine-2-carbaldehyde as a white solid (0.86 g, 61%). ¹H NMR (CDCl₃) δ 6.59 (m, 1H), 6.92 (m, 2H), 7.60 (m, 1H), 7.76 (d, 1H, J=7.5 Hz), 8.88 (d, 1H, J=3.5 Hz), 10.11 (s, 1H).

References:

US2004/209921,2004,A1 Location in patent:Page 41