Pyrimidine-5-boronic acid pinacol ester

General procedure: A stream of nitrogen was passed through a suspension of aryl bro-mide (0.18 mmol), the appropriate boronic acid pinacol ester(0.25 mmol), 2 M Na 2 CO 3 (0.26 mL) and DMF (2 mL) for 10 min.PdCl 2 dppf (8 % mol) was then added and the reaction was warmed to 80 C and stirred under nitrogen for 3 h. When the reaction was com-plete, the mixture was cooled to room temperature and extracted withethyl acetate (3 × 15 mL). The combined ethyl acetate extracts weredried with sodium sulfate and dried under vacuum to give a residuethat was purified by chromatography column using a gradient of ethylacetate/n-hexane (10:90 to 50:50) to afford the desired compounds.General procedure: A mixture of intermediate 1103 (2.00 g, 5.02 mmol) and 4-chlorophenylboronic acid [1679-18-1] (706 mg, 4.52 mmol) in THF (40 mL) was degassed with nitrogen for 10 min. [l, l'-Bis(diphenylphosphino)ferrocene]dichloropalladium, complex with dichloromethane (410 mg, 0.50 mmol) and potassium carbonate (2.0 M in H20, 7.53 mL, 15.1 mmol) were added and the reaction mixture was stirred at 70C for 18 h. The reaction mixture was poured out into water and the precipitated was filtered off. The solid was dried under vacuum at 60C to afford intermediate 1119 (2.2 g, 92%). The product was sued in the next step without further purification Intermediate 1144 (3.4g) was synthesized from intermediate 1103 and 5-pyrimidineboronic acid pinacol ester [321724-19-0] according to the procedure reported for the synthesis of intermediate 1119 with a shorter reaction time of 3 h.General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120°C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used).General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120°C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used).General procedure: Under N2 atmosphere, a mixture of 6 (100.0 mg, 0.26 mmol), Pd(pph3)4 (30.0 mg, 0.026 mmol), 2.0M aq Na2CO3 (0.29 ml, 0.78 mmol) and 1-Methyl-1H-pyrazole-5-boronic acid pinacolester (108.2 mg, 0.52 mmol) in 1, 4-Dioxane (0.65 ml) was heated to90 C and stirred for 6 h. The reaction mixture was cooled, dilutedwith ethyl acetate, washed with water, dried over anhydrousNa2SO4, filtered and concentrated under vacuum. Purification onsilica using a solvent gradient of 10-30% ethyl acetate in hexanesyielded the desired compound 1j (77.0 mg, 77.5%). Compounds 1akwere prepared according to general procedure as described forcompound 1j using corresponding aryl bromide 2-4 and theappropriate boronic acid or boronic acid pinacol ester. The characterizationdata for compounds 1a-k were provided below.

2-Methoxyphenylborornic Acid Pinacol Ester is used in the preparation of indole derivatives as selective inhibitors of all three members of the Pim kinase family. It is also used to prepare inhibitors of TGF-β1 and activin A signalling.

Molecular Weight:206.05
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:206.1226579
Monoisotopic Mass:206.1226579
Topological Polar Surface Area:44.2
Heavy Atom Count:15
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes