2-FLUORO-6-(TRIFLUOROMETHYL)BENZONITRILE

2-Fluoro-6-(trifluoromethyl)benzonitrile (10 g, 0.053 mol) was warmed at 40C in 200 ml of anhydrous methylamine in an autoclave for 2 days. The excess methylamine was allowed to evaporate and the resulting grey solid was dissolved in 200 ml of methylene chloride together with 4-aminopyridine (0.1 g, 0.001 mol) and triethylamine (3.3 ml, 0.026 mol). To the chilled solution was slowly added ethyl malonyl chloride (8.8 g, 0.060 mol). The solution was stirred for 4 hours and then worked up to give a yellowish syrup. The syrup was dissolved in 100 ml of anhydrous ethanol, and sodium methoxide (5.4 g, 0.10 mol) was added. After 1 hour, the solvent was removed and the residue worked up with methylene chloride and water. The quinoline derivative formed was carefully dried and suspended in 250 ml of chilled anhydrous tetrahydrofuran. Sodium hydride (4 g, 0.125 mol) was slowly added and then methyl iodide (10 ml, 0.15 mol). The mixture was heated under reflux for 6 hours, quenched with water and worked up with diethyl ether. The solvents were removed and the residue (17.3 g) was dissolved in a mixture of ethanol (50 ml) and conc. hydrochloric acid (10 ml). The solution was warmed at 45C overnight, cooled and the precipitate was collected to give 8 g of the title compound, yield 48 %. 1H NMR delta (CDCl3) delta 1.46 (3H, t), 3.68 (3H, s), 4.50 (2H, q), 7.58 (1H, m), 7.71 (2H, m), 15.0(1H, s).Example 46 2-(2-Methyl-4-pyrrolidin-1-yl-quinolin-7-ylmethoxy)-6-trifluoromethyl-benzonitrile The title compound was produced in accordance with the general method of example 6 from (2-methyl-4-pyrrolidin-1-yl-quinolin-7-yl)-methanol (example 2) and xvii) 4-(Trifluoromethyl)benzo[d]isoxazol-3-amine I42 [84] To a solution of acetohydroxamic acid (2.25 g, 30 mmol) in DMF (80 ml.) at 0 C under N2 was added t-BuOK (3.37 g, 30 mmol) and the mixture was heated at 30 C for 1 h. A solution of In a sealed tube, a mixture of 2- fluoro-6-(trifluoromethyl)benzonitrile (4.5 g, 23.8 mmol) and guanidine carbonate (8.57 g, 47.6 mmol) in DMA (54 ml_) was stirred at 130 C for 3h. The reaction mixture was cooled to rt, diluted with EtOH and the solvent was removed under reduced pressure. The residue was mixed with cold water and the solid was isolated by filtration to give the title compound as a tan solid (5.2 g), and was used in the next step without further purification.8 g of anhydrous potassium fluoride was added to 50mL of N, N-dimethylformamide and stirred at room temperature.

Molecular Weight:189.11
XLogP3:2.6
Hydrogen Bond Acceptor Count:5
Exact Mass:189.02016175
Monoisotopic Mass:189.02016175
Topological Polar Surface Area:23.8
Heavy Atom Count:13
Complexity:226
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes