2-METHYLPYRIDINE-4-BORONIC ACID PINACOL ESTER

To a previously degassed solution of 4-bromo-2-methylpidine (0.500 g, 2.906 mmol), 4, 4, 4’, 4’, 5, 5, 5’, 5’-octamethyl-2, 2’-bi( 1 , 3, 2-dioxaborolane) (0.812 g, 3.997 mmol), potassium acetate (0.854 g, 8.720 mmol) in 1, 4-dioxane (5mL) in 50 mL sealed tube was added [1, 1 ‘-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (0.021 g, 0.029 mmol) and stirred at 80°C 4 h. Evaporated off the solvent and purified column chromatography on silica gel (ethyl acetate pet ether = 3070) to give the titledcompound (0.250 g, 39percent) as a off white solid .LCMS: mlz 220.1 [M+H] .To a mixture of 6-((6-chloropyridin-3-yl)methyl)-3-(trans-2-hydroxycyclopentyl)-7, 8-dimethylquinazolin-4(3H)-one (0.10 g), General procedure: A solution of 5-bromo-2, 3-dihydro-1H-inden-4-amine (Intermediate R4, Step E) (500 mg, 2.36 mmol), pyridin-4-ylboronic acid (348 mg, 2.83 mmol), K2CO3(1.075 g, 7.78 mmol) and Pd(dppf)Cl2.DCM (385 mg, 0.472 mmol) in 1, 4-dioxane (18 mL) and water (3.6 mL) was degassed with N2 for 10 min. The reaction was stirred at 85C for 4 h, cooled to RT and filtered through celite, washing with EtOAc (100 mL). The filtrate was concentrated in vacuo and purified by chromatography on silica gel (24 g column, 0-10% MeOH/DCM) to afford the title compound (400 mg, 77%) as a dark brown solid. LCMS m/z 211.1 (M+H)+(ES+).1H NMR (DMSO-d6) d 8.62 - 8.56 (m, 2H), 7.45 - 7.39 (m, 2H), 6.87 (d, J = 7.6 Hz, 1H), 6.60 (d, J = 7.6 Hz, 1H), 4.70 (s, 2H), 2.84 (t, J = 7.5 Hz, 2H), 2.71 (t, J = 7.4 Hz, 2H), 2.03 (p, J = 7.5 Hz, 2H).A solution of K2CO3 (1356 mg, 9.81 mmol) in water (2 mL) was added to 5-bromo-2, 3- dihydrobenzofuran-4-amine (Intermediate C5, Step B) (700 mg, 3.27 mmol) in dioxane (8 mL) followed by 2-methyl-4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2- yl)pyridine (716 mg, 3.27 mmol). The mixture was degassed with N2andPd(dppf)Cl2.DCM (134 mg, 0.164 mmol) was added. The reaction was then heated to 80C for 20 h, cooled to RT and partitioned between DCM (30 mL) and water (20 mL). The organic phase was dried (phase separator) and concentrated in vacuo. The product was purified by chromatography on silica gel (24 g column, 0-100% EtOAc/isohexane) to afford the title compound (492 mg, 63%) as a tan solid.LCMS m/z 227.2 (M+H)+(ES+).1H NMR (DMSO-d6) d.8.41 (d, J = 5.2 Hz, 1H), 7.24 (s, 1H), 7.18 (dd, J = 5.2, 1.7 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.14 (d, J = 8.1 Hz, 1H), 4.90 (s, 2H), 4.54 (t, J = 8.7 Hz, 2H), 3.01 (t, J = 8.7 Hz, 2H), 2.48 (s, 3H).8-(2-Methylpyridin-4-yl)-7-phenyl-[1, 2, 4]triazolo[4, 3-c]pyrimidin-5-amine 12 Compound 2c (100 mg, 0.345 mmol), In practice, the first intermediate product is added to the vessel from 0.3 millimoles to 12 millimoles.0.1 ml to 5.9 mmol of the third reactant is added with an appropriate amount of toluene and potassium carbonate aqueous solution.0.001 mmol-0.99 mmol of tetrakistriphenylphosphorus palladium was added in two portions under an argon atmosphere.Reaction at 90 degrees Celsius - 120 degrees Celsius for 9 hours - 36 hours, Obtaining a mixture comprising the electroluminescent material, and then separating and purifying to obtain the electroluminescent material[l, -bis(dicyclohexylphosphino)ferrocene]dichloropalladium(II) (110 mg, 10 mol%) was added to a mixture of 8-bromo-7-chloroimidazo[l, 2-c]pyrimidin-5-amine (prepared in Example 1, Step 3) (370 mg, 1.5 mmol), 2-methyl-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan- 2-yI)pyridine (490 mg, 2.2 mmol), and cesium carbonate (1.5 g, 4.5 mmol) in fcrt-butanoi (8.3 mL) and water (1.7 mL). The solution was purged with nitrogen, and then stirred at 75 C for 5 h. The reaction mixture was cooled to room temperature and filtered through a Celite plug with EtOAc. The filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column eluting with 0-10% MeOH/DCM to give the desired product, which was used in the next step without further purification. LC-MS calculated for C12H1 1CIN5 (M+H)?: m/z = 260.1 ; found 260.0.[l, l?-bis(dicyclohexylpliosphino)ferrocene]dichloropalladium(II) (0.41 g, 10 mol%) was added to a mixture of 5-bromo-2-methoxy-6-phenylpyrimidin-4-amine (1.5 g, 5.4 mmol), 2-methyl-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (1.8 g, 8.0 mmol), and cesium carbonate (3.5 g, 11 mmol) in te/7-butanol (20 mL) and water (3.9 mL). The solution was purged with nitrogen, and then stirred at 120 C for 1.5 h. The reaction mixture was cooled to room temperature, filtered through a Celite plug with DCM and concentrated under reduced pressure. Water (100 mL) was added to the residue and the resulting solid was collected by filtration then dried to give the desired product (1.02 g, 65 %), which was used in the next step without further purification. LC-MS calculated for CHHITN+O (M+H)+: m/z = 293.1; found 293.1.Under a nitrogen atmosphere, 2-methyl-4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) pyridine (10.0 g), 3, 5-dibromopyridine (11. 0g), A flask containing Pd (PPh3) 4 (1.0 g), potassium phosphate (19.0 g) and N, N-dimethylacetamide (200 ml) was stirred at reflux temperature for 6 hours.After cooling the reaction solution to room temperature, To remove catalyst metal ions, A solution prepared by dissolving ethylenediaminetetraacetic acid / tetrasodium salt dihydrate in an amount of about 3 times mol of the target compound in an appropriate amount of water and ethyl acetate were added to separate the layers.The solvent was distilled off under reduced pressure and purified by amino group-modified silica gel column chromatography (toluene / heptane = 1/4 (volume ratio))5-Bromo-2'-methyl-3, 4'-bipyridine(3.2 g) was obtained.A solution of methyl 2-bromo-3-isopropyl-lH-indole-5-carboxylate (0.400 g, 1.351 mmol), 2-methyl-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (0.621 g, 2.84 mmol) and cesium carbonate (1.320 g, 4.05 mmol) in dioxane (10.00 mL) and water (2.500 mL) was degassed for 30 min. Next, PdCPhsPH (0.312 g, 0.270 mmol) was added and the reaction mixture was stirred at 90 C for 16 h. Crude LCMS showed formation of product and no starting material. The reaction was quenched with water (5 mL). The reaction mixture was extracted with DCM (2 X 40 mL), the combined organic extracts were washed with brine (10 mL), dried (NaaSOr) and concentrated to get crude compound. The crude material was purified by column chromatography using 40 g silica column, compound was eluted m ethyl acetate, the fractions were collected and concentrated to afford methyl 3-isopropyl-2-(2-methylpyridin-4-yl)-lH-indole-5- carboxylate (0.550 g, 0.856 mmol, 63 % yield) as a gummy solid. LCMS retention time 0.76 min [G] MS m/z: 309.6 { .VI H );

Molecular Weight:219.09
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:219.1430590
Monoisotopic Mass:219.1430590
Topological Polar Surface Area:31.4
Heavy Atom Count:16
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes