5-Bromo-2-methoxybenzonitrile

off-white crystalline

General procedure: To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 molpercent, 0.02 mmol) and CHExample 34 Example 34 Example 37 Example 34 5-Bromo-2-(methyloxy)benzonitrile 5-Bromo-2-methoxybenzaldehyde (20.00 mmol, 4.30 g) was dissolved in formic acid (20 mL) and treated with hydroxylamine hydrochloride (21.00 mmol, 1.45 g) and sodium acetate (26.00 mmol, 2.13 g). The reaction mixture was heated at reflux for 15 hours. The solvent was removed under reduced pressure and the residue was taken up in ethyl acetate (250 mL). The organics were washed with saturated sodium bicarbonate solution (2.x.200 mL) and then dried with MgSOCompound 64 (E)-Methyl 3-(3-(N-((3'-cyano-4'-methoxy-[l, l'-biphenyl]-4- yl)methyl)cyclohexanecarboxamido)phenyl)acrylate [00430] A mixture of Intermediate 16 (500 mg, 0.99 mmol), Reference Example 26 [Step a] To a solution of compound 1 (3.00 g, 14.1 mmol) in N, N-dimethylformamide (30.0 mL) were added sodium azide (4.60 g, 70.7 mmol), pyridine hydrochloride (3.27 g, 28.3 mmol), and the mixture was stirred with heating at 130°C for 2 hr. The reaction solution was allowed to cool to room temperature, water (200 mL), 1 M-hydrochloric acid were added to adjust to pH 4 - 5, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel chromatography to give compound 2 (682 mg, 18.9percent). MS(ESI)m/z: 255, 257(M+1)+.[0332] 2-Fluoro-5-iodobenzonitrile (0.41 mg, 1.7 mmol), triphenylphosphine (0.088 g, 0.33 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.076 mg, 0.084 mmol) were dissolved in THF (15 ml) and flushed with nitrogen. Themixture was treated with 1-(4-ethynyl-4-hydroxypiperidin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone (520 mg, 1.7mmol) followed by tetrabutylammonium fluoride solution in THF (1.0 M, 3.3 ml, 3.3 mmol), sealed and placed in an oilbath at 60 °C for 3 h. The mixture was cooled, diluted with water and ethyl acetate, and the layers separated. After theaqueous was extracted with additional ethyl acetate (2x), the combined organics were washed successively with water(2x) and brine, dried (Na2SO4) and concentrated. The resulting residue was purified by MPLC (eluent gradient 10->50percentEtOAc:hex.) to provide 2-fluoro-5-[(4-hydroxy-1-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperidin-4-yl)ethynyl]benzonitrile:_[0354] 5-[(4-Hydroxy-1-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperidin-4-yl)ethynyl]-2-methoxybenzonitrile was preparedin a similar fashion to that described for the synthesis of EXAMPLE 10 starting from 1-(4-ethynyl-4-hydroxypiperidin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone and General procedure: A mixture of aryl halide (1.0 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2.0 mmol), novel ligand (0.1 mol percent, 0.5 mg), and Pd(OAc)2 (0.1 molpercent, 0.23 mg) was heated in water (5 ml) at 80 °C temperature. The progress of the reaction is monitor by TLC. After the completion of the reaction, ethyl acetate (10 ml) was added to the reaction mixture and extracted with ethyl acetate (3 x 10 ml). The combined organic layer was dried with anhyd. Na2SO4 and the solvent were concentrated in vacuum to obtain a light yellow-white solid. The residue was purified by silica gel column chromatography (5-10percent EtOAc in hexane) to afford the corresponding pure products.General procedure: A mixture of aryl halide/tosylate (1.0 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2.0 mmol), ligand (0.1 molpercent) and Pd(OAc)2 (0.1 molpercent) in EtOH (5 mL) was stirred at r.t. The progress of the reaction was monitored by TLC. Upon completion of the reaction, solvent was removed under reduced pressure. Water (10 mL) was added to the reaction mixture and extracted with EtOAc (3 × 10 mL). The combined organic layer was dried with anhydrous Na2SO4 and the solvent was concentrated in vacuum to obtain a light yellow-white solid. The residue was purified by silica gel column chromatography (EtOAc'hexane, 5'10percent) to afford the corresponding pure products.A 1 M solution of lithium bis-hexamethylsilazide (220 mmol, 220 mL) in tetrahydrofuran was transferred into a 3 neck round bottom flask. The solution was cooled to 0° C. and treated dropwise with EXAMPLE II A mixture of 4.0 g EXAMPLE II STR32 A mixture of EXAMPLE II STR35 A mixture of EXAMPLE II STR22 A mixture of

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