Electric Literature of 1822-51-1, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 1822-51-1 as follows.
Example 62: 6-(Pyridin-4-yl-methyl)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl- phenvD-amide; A mixture of 22.4 mg (0.10 mMol) Pd(O2CCH3)2) 52.6 mg (0.20 mMol) triphenylphosphine, 151 mg (0.33 mMol) 6-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-naphthalene-1- carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide and 229.3 mg (1.08 mMol) K3PO4 in 3 ml toluene is degassed repeatedly by evaporation and flushing with N2. Then 59 mg (0.36 mMol) 4-chloromethyl-pyridine hydrochloride are added and the mixture is stirred at 80 0C for 20 h, when additional 18.5 mg (0.082 mMol) Pd(O2CCH3)2 and 43.1 mg (0.164 mMol) triphenylphosphine are added. After 3 h at 110 0C the reaction mixture is poured into water and EtOAc. The aqueous phase is separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography [Combi Flash; CH2CI2 ? CH2CI2/(Me0H + 10 % NH3aq) 9:1] gives the title compound: MS: [M+1]+ = 425; HPLC: AtRe( = 12.7.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1822-51-1, its application will become more common.
Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2006/59234; (2006); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem