4-Borono-3-chlorobenzoic acid

To a suspension of 4-(5-benzyl-2, 6-dimethoxypyrimidin-4-yl)cyclohex-l-en-l-yl trifluoromethanesulfonate (Intermediate J-l) (0.165 g, 0.360 mmol) and 4-borono-3- chlorobenzoic acid (0.079 g, 0.396 mmol) in dioxane (3 mL) was added a solution of sodium carbonate (0.084 g, 0.792 mmol) in water (0.5 mL). The mixture was degassed with bubbling N2 for 5 minutes. l, r-Bis(diphenylphosphino)ferrocene-palladium(II)di chloride dichloromethane complex (Pd(dppf)Cl2) (29 mg, 0.036 mmol) was added and the mixture was heated at 80C for 1 hour 15 minutes. The reaction was cooled to room temperature and partitioned between aqueous NELCl solution (10 ml) and EtOAc (10 ml). The layers were separated and the aqueous layer was extracted with EtOAc (2 x 10 mL). The organic extracts were combined, dried over MgS04 and concentrated in vacuo. The crude product was purified by chromatography on silica gel (4 g column, 0-50% EtO Ac/isohexane) to afford the title compound 4'-(5-benzyl-2, 6-dimethoxypyrimidin-4-yl)-2-chloro-2', 3', 4', 5'-tetrahydro- [l, l'-biphenyl]-4-carboxylic acid (0.117 g, 0.239 mmol, 66.4 % yield) as a white solid. Analytical data: Rl 3.17 min (Method 1); m/z 465 (M+H)+ (ES+).General procedure: Different substituted phenylboronic acid compounds B28-B32and B43-B47 (1.0 mmol, 1.0equiv), sodium azide (1.5 mmol, 1.5equiv) and copper sulphate pentahydrate (0.1 mmol, 0.1equiv)were mixed in 10 mL methanol and stirred at room temperature for12 h. Then, the reaction solvent was removed under reducedpressure and 20 mL of water was added. The mixturewas extractedby dichloromethane (DCM, 3 20 mL), the combined organic phasewas dried over anhydrous Na2SO4, filtered, and concentrated toafford the crude azide substituents N28eN32 and N43eN47, which was used for the next step directly.[0477] Step 1: Synthesis of 4-(5-bromopyridin-3-yl)-3-chlorobenzoic acid. 3, 5-dibromopyridine (0.5 g, 2.11 mmol, 1 equiv), 4-carboxy-2-chlorophenyl boronic acid (0.402 g, 2.00 mmol, 0.95 equiv) and sodium carbonate (0.559 g, 5.28 mmol, 2.5 equiv) in DME-H2O (3.75:1.25 mL) were combined in a 10 mL glass seal tube and purged with nitrogen gas for 10 minutes. After adding palladium tetrakis (0.122 g, 0.105 mmol, 0.05 equiv) the mixture was again purged with nitrogen gas for 10 minutes. The mixture was heated to 80 C for 16 h and reaction monitored by TLC and LCMS. After completion, the reaction mixture was cooled to RT, 10 mL water was added and the whole was extracted with EtOAc (3x15 mL). The organic extracts were combined and washed with brine (3x10 mL) and dried over anhydrous sodium sulfate. The extract was then concentrated under reduced pressure to give crude 4-(5-bromopyridin-3-yl)-3-chlorobenzoic acid (0.350 g, crude) as a white solid.

suzuki reaction

Molecular Weight:200.38
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:200.0047665
Monoisotopic Mass:200.0047665
Topological Polar Surface Area:77.8
Heavy Atom Count:13
Complexity:199
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes