2-[(3-fluorophenyl)amino]isonicotinonitrile synthesis

Yield:137225-10-6 75%

Reaction Conditions:

with palladium diacetate;caesium carbonate;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl in 1,4-dioxane at 80; for 4 h;Sealed tube;Inert atmosphere;Buchwald-Hartwig Coupling;

Steps:

3j 2-((3-fluorophenyl)amino)isonicotinonitrile

General procedure: General Procedure: An oven-dried test tube equippedwith a magnetic stir bar was charged with 2-chloroisonicotinonitrile (69 mg,0.5 mmol), Pd(OAc)₂ (2.25 mg, 2 mol%), BINAP (9.38 mg, 3 mol%) , theamine if solid (1.0 mmol), and Cs₂CO₃ (228 mg, 1.0 mmol).The vessel was then sealed, evacuated, and backfilled with argon (this sequencewas carried out a total of three times). 1,4-dioxane (2.0 mL) and the amine ifliquid (1.0 mmol) via syringe was added successively under an argon atmosphere., and the solution was heated up to 80°C for 4 h in an oil bath. The reactionmixture was allowed to cool to r.t. diluted with dichloromethane, and washed once each withwater and brine, dried over Mg₂SO₄, filtered, andconcentrated in vacuo. The crude product was then purified by silicagelchromatography mixture of pentane and Et₂O or mixture of pentane andethyl acetate. The products were characterized by ¹H NMR, ¹³CNMR and LC-MS.

References:

Guo, Shuo;Wang, Yaping;Sun, Chunxia;Li, Jingya;Zou, Dapeng;Wu, Yangjie;Wu, Yusheng [Tetrahedron Letters,2013,vol. 54,# 25,p. 3233 - 3237] Location in patent:supporting information