2-(5-bromopyridin-2-yl)acetic acid

5-(Bromo-pyridin-2-yl)-acetic acidTo a solution of 2-(5-Bromo-pyridin-2-yl)-malonic acid diethyl ester (16.6 g, 52.5 mmol) in MeOH (200 mL) was added aq. NaOH (2N, 105 mL, 210 mmol). The solution was stirred at room temperature for 3 h, then concentrated in vacuo. The residue was dissolved in water and neutralized with 2N HCl to pH 3-4. Then the solid was filtered and washed with water, ether, dried to give a white solid product without further purification (9.0 g, 80percent). MS: calc'd 215 (MH+), exp 215 (MH+).To a solution of diethyl 2-(5-bromopyridin-2-yl)malonate 166 (2.1 g, 6.6 mmol) in MeOH (30 mL) was added 2 M NaOH aqueous solution (14 mL, 28 mmol). The resulting mixture was stirred at room temperature for 3 hours. The solution was concentrated under reduced pressure and the residue was dissolved in water (20 mL). The pH of the solution was adjusted to 3-4 by addition of 6 M HCI. The white precipitate formed was collected by filtration, washed with water and dried at 50 °C to give the title compound as a white solid (1 .0 g, 70percent). LCMS-C: RT 0.78 min; m/z 216.0 [M+H]4'-Amino-2', 6'-dichloro-4-isobutyl-[1, 1'-biphenyl]-3-carbonitrile (100 mg, 0.31 mmol), 2-(5-Bromopyridin-2-yl)acetic acid (200 mg, 0.93 mmol), 4-fluoroaniline (103 mg, 0.93 mmol), HATU (353mg, 0.93mmol)After stirring with TEA (188 mg, 1.86 mmol) in DMF (10 mL) at room temperature for 2 h, Water (50 mL) was poured and extracted with ethyl acetate (2×50 mL).The organic phase was separated and washed with saturated aqueous NaCl (2×).The organic phase was separated and dried over anhydrous Na 2 SO 4Filter and concentrate, and the residue was purified by silica gel column chromatography.Elution with ethyl acetate/petroleum ether (1:3) gave the desired compound 18 (250 mg, 87%).Compound 3 (0.2 g, 0.76 mmol, 1.0 eq), Compound 4 (182 mg, 0.84 mmol, 1.1 eq) was dissolved in DMF (5 mL). Then, HATU (433 mg, 1.14 mmol, 1.5 eq) was added, followed by DIEA (386 mg, 3.04 mmol, 4.0 eq), and allowed to react at room temperature for 16 hours. TLC showed little residue of compound 3, EA (10 mL), water was added and the organic phase was separated. The organic phase was washed with water, brine, dried over anhydrous sodium sulfate, and rotary evaporation under reduced pressure to give compound 5 (200mg, yield: 76%).At room temperature, Compound 9 (0.18 g, 0.56 mmol, 1.0 eq), 10 (0.134 g, 0.62 mmol, 1.1 eq), HATU (0.319 mg, 0.84 mmol, 4.0 eq) was added to 20 mL DMF. Stirred for 5min, added DIEA (0.289mg, 2.2mmol, 4.0eq), stirred at room temperature for 2h. The reaction was monitored by TLC, and 30 mL of EA and 50 mL of water were added to the mixture. The liquid phase was separated, and the aqueous phase was extracted three times with 50 mL of EA. The organic phase was combined, and the organic phase was washed with water and saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate. The mixture was dried under reduced pressure and passed through a column (PE: EA = 20:1 to 5:1) to afford compound 11 (0.18 g, yield: 63%).At room temperature, Compound 8 (0.72 g, 2.47 mmol, 1.0 eq), 9 (0.53 g, 2.47 mmol, 1.0 eq) was added to 20 mL DMF. After stirring for 5 min, DIEA (1.27 g, 9.9 mmol, 4.0 eq) was added and stirred at room temperature for 6 hours. The reaction was monitored by TLC, and 30 mL of EA and 50 mL of water were added to the mixture. The liquid phase was separated, and the aqueous phase was extracted three times with 50 mL of EA. The organic phase was combined, and the organic phase was washed with water and saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate. The mixture was spin-dried under reduced pressure to give compound 10 (0.70 g, yield: 58%).

Molecular Weight:216.03
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:214.95819
Monoisotopic Mass:214.95819
Topological Polar Surface Area:50.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes