4-Bromo-3-methoxybenzonitrile

To a solution of 4-bromo-3-methoxyaniline (1k) (2.00 g, 9.9 mmol) in water (50 mL) was added hydrochloric acid (4 mL) and sodium nitrite , NaNO2) (0.75 g, 10.9 mmol) is slowly added at 0°C. The mixture was stirred at 0 °C for 30 minutes and then potassium carbonate (1.67 g, 11.9 mmol), copper cyanide (CuCN) (1.06 g, 11.9 mmol) and potassium cyanide (KCN) Mmol) dissolved in water (50 mL). The mixture is stirred at 70°C , cooled, and extracted with toluene. Magnesium sulfate is added to the extracted organic layer to remove water and concentrated under reduced pressure. The concentrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ether = 6: 1) , 4-bromo-3-methoxybenzonitrile can be obtained in the form of yellow powder.General procedure: 4-Methoxy-N-(4-(piperazin-l-yl)phenyl)benzamide (120 mg, 0.39 mmol), the R2- (Het)aryl halide (1.1 eq.), CS2CO3 (2.2 eq., 276 mg, 0.85 mmol), [Pd(OAc)2] (0.1 eq., 9 mg, 0.04 mmol) and RuPhos (0.2 eq., 36 mg, 0.08 mmol) were combined in a reaction tube. De gassed dioxane (3 ml) was then added, the reaction tube flushed with nitrogen, sealed and the reaction mixture was stirred at 80 C overnight. In case of incomplete conversions more rea gents were added accordingly. After completion the reaction mixture was cooled to rt and H20 added. The precipitate formed was collected by filtration, washed with H2O and dried. The residue was dissolved in DCM/MeOH (2:1), adsorbed onto HM-N beads (Biotage) and evaporated. The resulting material was dry-loaded onto a silica column and purified by flash column chromatography eluting with 0.5 to 3% methanol / dichloromethane to afford the title compounds as yellow solids.Yield: 47 mg. NMR (400 MHz, DMSO): d 9.92 (s, 1H), 7.95 (d, J=8.8 Hz, 2H), 7.63 (d, J=9.2 Hz, 2H), 7.38 (s, 2H), 7.07 - 7.03 (m, 3H), 6.99 (d, J=9.2 Hz, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 3.25 (s, 4H) 4H-piperazine hidden under DMSO peak. LC-MS: Rt = 3.36 min, m/z = 443 [M+H]+.Compound 2-methyl-6-tributylstannylpyridine (360 mg, 0.94 mmol), To a solution of 4-chloro-2-fluorophenylboronic acid (20 g, 114 mmol) in 1, 4- dioxane and water (400 mL/40 mL, v/v) was added sodium carbonate (36 g, 342 mmol), Pd(Ph3P)4 (7.0 g, 6.0 mmol), and

Molecular Weight:212.04
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:210.96328
Monoisotopic Mass:210.96328
Topological Polar Surface Area:33
Heavy Atom Count:11
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes