2,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Intermediate 24:-dichloro-4-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyridineUnder an atmosphere of nitrogen, a mixture of 2, 6-dichloropyridine (3g, 20.3mmol), 4, 4, 4To a mixture of 2, 6-dichloropyridine (3.28 g, 22.2 mmol) and bis (pinacolato) diboron (6.2 g, 24.4 mmol) was added 1, 10-phenanthroline (0.24 g, 1.3 mmol) and CHLORO-1, 5-cyclooctadiene iridium (I) dimer (0.44 g, 0.66 mmol) under nitrogen followed by anhydrous 1, 2- dichloroethane. Nitrogen was bubbled through the mixture for 5 minutes and the reaction was then heated with stirring at 100 °C for 15 hours under an atmosphere of nitrogen. The mixture was allowed to cool to room temperature, poured onto DIETHYLETHER/4N sodium hydroxide (50 ml/200 ml) and the phases separated. The aqueous phase was acidified with 6N hydrochloric acid and the resulting solid was filtered, washed with water and dried on the sinter to yield the pinacol ester of 2, 6-dichloropyridin-4-ylboronic acid (3.5 g, 58 percent) as a grey solid.Example 42, 6-Dichloropyridine (20.3 mmol, 3.0 g), bis-(pinacolato)diboron (22.3 mmol, 5.66 g) and 1, 10-phenantroline (1.2 mmol, 0.212 g) were dissolved in dry 1, 2- dichloroethane (100 ml) , degassed and purged with Ar for 5 minutes. Chloro-1, 5- cyclooctadiene iridium(I) dimer (0.445 g, 0.7 mmol) was added and the resulting reaction mixture was stirred at 100°C for 15 hours in sealed tube conditions. Aftercompletion of the reaction the contents were cooled, filtered through Celite and 1, 2- dichloroethane was evaporated with vacuum. The crude residue was dissolved in diethyl ether and washed with sodium hydroxide (4N solution in water). The aqueous layer was acidified to pH=1 with HC1 (6N solution in water) and resulting solid was filtered off and washed with water. 4.8 g of the title compound was obtained as a grey solid.Example 18.N-(3-fluoro-6’-(5-( 1-methyl-i H-pyrazol-4-yl)-1H-bzd[d}iniidazo1 i-yl)-[2, 4’-bipyridinj-2-yl)cyclopropaiiesulfonamide. .a) 2, 6-Dichloro-4-(4, 4, 5, 5-tetramethyl- 1 , 3, 2-dioxaborolan-2-yl)pyridine. A solution of 2, 6-dichloro-4-iodopyridine (15 g, 54.9 mmol) in DMF (150 ml)was degassed by N2 bubbling for 5 mm. Bispinacolato diborane (17.63 g, 82.4 mrnol, 1.5 eq) was added and the mixture was degassed for another 5 mm. Pd(dppf)C12 (2.24 g, 2.7 mmol, 0.05 eq) and potassium acetate (8.07 g, 82.4 mmol, 1.5 eq) were addedsequentially using the procedure of Intermediate and the mixture was then heated at 90 °C for 3 h. The reaction mixture was then quenched and extracted as in Intermediate Example 1. The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50 percent ethyl acetate in hexane) to afford the title product in 67 percent yield (10 g). 1H NMR (300 MHz, CDCl3)o7.59 (s5 2H), 1.35 (s, 611), 1.26 (s, 6H).Description 6 2*6-DICHLORO-4-(3-METHVL-2-PYRIDYL) PERIDINE To a mixture of 2, 6-dichloropyridine (3.28 g, 22.2 mmol) and bis (PINACOLATO) diboron (6.2 g, 24.4 mmol) was added 1, 10-phenanthroline (0.24 g, 1. 3 mmol) and CHLORO-1, 5-CYCLOOCTADIENE iridium (I) dimer (0.44 g, 0.66 mmol) under nitrogen followed by anhydrous 1, 2-dichloroethane. Nitrogen was bubbled through the mixture for 5 min and the reaction was then heated with stirring at 100 C for 15 h under an atmosphere of nitrogen. The mixture was allowed to cool to room temperature, poured onto DIETHYLETHER/4N sodium hydroxide (50 ML/200 ML) and the phases separated. The aqueous phase was acidified with 6N hydrochloric acid and the resulting solid was filtered, washed with water and dried on the sinter to yield pinacol 2, 6-dichloropyridine-4-boronate (3.5 g, 58 percent) as a grey solid, MS: (ES (M+1)) 274/276. LH NMR (360 MHz, DMSO) 8 1.30 (12H, s), 7.57 (2H, s) ppmThe reaction liquid was cooled to 0 ° C, filtered, and the solvent was evaporated to dryness, and then sulfolane was added, and the intermediate was rectified to obtain 2, 6-dichloropyridine-4-(ditetrahydropyrrolyl)borate in a yield of 78percent.After heating and melting the pinacol (18.4 g, 0.16 mol), the temperature was 80-90 ° C, and the mixture was dropped into the above intermediate.During the dropwise addition, the tetrahydropyrrole formed was separated and completely exchanged. After cooling, the ethanol and n-heptane mixed solvent were beaten to obtain 38.9 g of a pale yellow solid, and the yield was 71percent.2, 6-Dichloro-4-pyridinol (6): The general process was applied to 2, 6-dichloropyridine (148 mg, 1.0 mmol). The borylation step was carried out with HBPin (200 mg, 1.55 mmol, 1.55 equiv.) and dmpe (3.0 mg, 0.02 mmol, 2 mol %) at 150 C. in cyclohexane for 3 hours (Ir-catalyzed borylation of the arene was previously described, see Cho et al., Science 295: 305-308 (2002)). The oxidation step was then performed after removal of cyclohexane as described above, after which the crude material was dissolved in ether and passed through a plug of silica gel (pentane/ether 2:1). Evaporation of solvent gave 145 mg material containing 108 mg phenol 6 (66%) and 37 mg water. Sublimation at 110 C. under 0.1 mmHg afforded analytically pure 6 as a white solid; mp 201-202 C. 1H NMR (300 MHz, acetone-d6): delta10.48 (brs, 1 H), 6.88 (s, 2 H); 13C NMR (75 MHz, acetone-d6): delta168.3, 151.5, 111.5; IR (KBr): 32002500 (br), 1597, 1576, 1554, 1427, 1294, 1211, 1157, 1092, 993, 966, 847 cm-1; LRMS: m/e 163 (M+), 128, 100. Anal. Calcd for C5H3Cl2NO: C, 36.62; H, 1.84; N, 8.54. Found C, 36.63; H, 1.98, N, 8.52. Another preparation of this compound was reported by Umemoto et al., Bull. Chem. Soc. Jpn. 64: 1081-1092 (1991) as a byproduct (mp not reported) during the hydrolysis of an N-fluoro-2, 6-dichloropyridinium PF6-salt that was prepared by the reaction of 2, 6-dichloropyridine with F2 gas with a 4% yield.A mixture of (l-bromovinyl)benzene (0.73 mg, 4.01 mmol), 2, 6-dichloro-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (1.1 g, 4.03 mmol), Pd(dppf)Cl2 (68 mg, 0.08 mmol), and potassium carbonate (1.1 g, 8.0 mmol) in dioxane/water (9 mL/3 mL) was treated and worked up as described in for Compound 52 to give 2, 6-dichloro-4-(l-phenylvinyl)pyridine (705 mg, 71% yield). The compound was confirmed with LC-MS only: 249.99 (M+H)+, C13H9CI2N.

Molecular Weight:274.0
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:273.0494642
Monoisotopic Mass:273.0494642
Topological Polar Surface Area:31.4
Heavy Atom Count:17
Complexity:275
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes