5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Pale yellow to brownish crystalline powder

Into a 500 ml single-mouth flask, successively add 5-bromoindole (20.00g, 0 . 1mol), bis(pinacolato)diboron (51.80g, 0 . 2mmol), potassium acetate (22.80g, 0 . 2mol), [ 1, 1 '-bis (diphenylphosphino) ferrocene] palladium dichloride (1.50g), and 350 ml dioxane. Under the protection of nitrogen, reflux for 8h. Cooling latter turns on lathe steams removing dioxane, with 200 ml distilled water dichloromethane is used for extraction after washing 3 times. Re-crystallization with methanol-methylene chloride to obtain the product 21.8g, the yield is 90percent.5-Bromoindole (2 g, 10.2 nmol) and Bis(pinacolato)diboron (4 g, 19.2 mmol) was dissolved in 1, 4-dioxane and then PdClUnder a nitrogen flow 5-bromo-1H-indole (100.0 g, 510.1 mmol), 4, 4, 4', 4', 5, 5, 5', 5'-octamethyl-2, 2'-bi (1, 3 , 2-dioxaborolane) (142.5 g, 561.1 mmol), Pd(dppf)ClUnder a nitrogen flow 5-bromo-1H-indole (25 g, 0.128 mol), 4, 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3 , 2-dioxaborolane) (48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55g, 0.383mol) and 1, 4-dioxane (500 ml) the mixture, and then the 130 in it was stirred for 12 hours.After the reaction was completed, the removal of water in our MgSO4 and then extracted with ethyl acetate, column chromatography (Hexane: ethyl acetate (EA) = 10: 1 (v / v)) to give 5- (4, 4, 5 a , 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H-indole (22.32 g, a yield of 72percent).Under a nitrogen stream, 5-bromo-1H-indole (25g, 0.128mol), 4, 4, 4′, 4′, 5, 5, 5′, 5′-octamethyl-2, 2′-bi(1, 3, 2-dioxaborolane)(48.58g, 0.191mol), Pd (dppf) Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol), and 1, 4-dioxane (500ml) mixed, and the mixture was stirred for 12 hours at 130°C .After completion of the reaction, and extracted with ethyl acetate, water was removed by MgSO4, column chromatography (hexane: EA = 10: 1 (v / v)) purified to at 5- (4, 4, 5, 5-tetra to give methyl 1, 3, 2-dioxaborolan-2-yl)-lH-indole (22.32g, 72percent yield).Under a nitrogen flow 5-bromo-1H-indole (25 g, 0.128 mol), 4, 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3 , 2-dioxaborolane) (48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) and 1, 4-dioxane (500 ml) and the mixture 130 ° Cin was stirred for 12 hours. After the reaction was terminated by the removal of water and then extracted with ethylacetate and MgSO4, purified by column chromatography (Hexane: EA = 10: 1 (v / v))purified 5- (4, 4, 5, 5-tetramethyl- by a 1, 3, 2-dioxaborolan-2-yl) -1H-indole (22.32g, a yield of 72percent).Under a nitrogen flow 5-bromo-1H-indole (25 g, 0.128 mol), 4, 4, 4', 4', 5, 5, 5', 5'-octamethyl-2, 2'-bi(1, 3, 2-dioxaborolane) (48.58 g, 0.191 mol), Pd(dppf)Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) and 1, 4-dioxane (500 ml) and the mixture at 130°C , It was stirred for 12 hours. After the reaction was terminated by the removal of water and then extracted with ethyl acetate and MgSO4, purified by column chromatography (Hexane: EA = 10: 1 (v / v)) 5-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-indole (22.32 g, a yield of 72percent).Under a nitrogen stream, 5-bromo -1H- indole (25g, 0.128mol), 4, 4, 4 ', 4', 5, 5, 5 ', 5'- octamethyl-2, 2'-bi (1, 3, 2-dioxaborolane) (48.58g, 0.191mol), Pd (dppf) Cl2 (5.2g, 5molpercent), KOAc (37.55g, 0.383mol), and 1, 4-dioxane (500ml) It was mixed, and the mixture was stirred for 12 hours at 130°C .After completion of the reaction, and extracted with ethyl acetate, water was removed by MgSO4, column chromatography (hexane:: EA = 10 1 (v / v)), 5- (4, 4, 5, 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-indole was obtained.(22.32g, 72percent yield).Under the nitrogen air 5-bromo-1H-indole (25 g, 0.128 mol), 4, 4, 4', 4', 5, 5, 5', 5'-octamethyl-2, 2'-bi(1, 3, 2-dioxaborolane) (48.58 g, 0.191 mol), pd(dppf)ClUnder a nitrogen flow 5-bromo-1H-indole ( 25 g, 0.128 mol), 4, 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3, 2-dioxaborolane) (48.58 g, 0.191 mol), Pd (dppf) Cl 2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol)and 1, 4-dioxane (500 ml) and the mixture 130 °C in was stirred for 12 hours. The reaction was terminated, and then extracted with ethyl acetate MgSOsynthesis of 5-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H- indole Under a nitrogen stream, 5-bromo--1H- indole (25g, 0.128mol) 4, 4, 4 ', 4', 5, 5, 5 ', 5'- octamethyl-2, 2'-bi (1, 3 , 2-dioxaborolane) (mixed 48.58g, 0.191mol), Pd (dppf) Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol), and 1, 4-dioxane (500ml) after, the mixture was stirred for 12 hours at 130 . After completion of the reaction, and extracted with ethyl acetate, water was removed by MgSO4, column chromatography [hexane: ethyl acetate (EA) = 10: 1 (v / v)] in purified 5- (4, 4, 5 to give 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-lH-indole (22.32g, 72percent yield).Under nitrogen, 5-bromo-1H-indole (25 g, 0.128 mol), 4, 4, 4', 4', 5, 5, 5', 5'-octamethyl-2, 2'-bi(1, 3, 2-dioxaborolane) (48.58 g, 0.191 mol), Pd(dppf)Cl2 (5.2 g, 0.05 mol), and potassium acetate (KOAc) (37.55 g, 0.383 mol) were dissolved in a round-bottomed flask filled with 1, 4-dioxane (500 ml). The mixed reactants were stirred for 12 h at 130 °C. After the reaction was terminated, the mixture was extracted with ethyl acetate three times. The organic layer was separated and the moisture was removed by drying over MgSO4. After removing the solvent by evaporation, the crude product was purified by column chromatography with an ethyl acetate and n-hexane (1:10) eluent. Yield 72percent (22.32 g), 5-bromo-1H-indole 25 g (128 mmol), 4, 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3, 2-dioxaborolane ) 48.58 g (0.191 mmol), Pd (dppf) Cl(25 g, 0.128 mol), 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3, Dioxane (500 ml) were mixed and heated at 130 for 12 hours at 130 . The resulting mixture was stirred at 130 for 2 hours to obtain a mixture of d- (2-dioxaborolane) (48.58 g, 0.191 mol), d After completion of the reaction, the reaction mixture was extracted with ethyl acetate, the water was removed with MgSO 4, and the residue was purified by column chromatography to obtain 5- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2 -yl) -1H-indole (22.32 g, yield 72percent).Under a nitrogen stream, 5-bromo-1H-indole (25g, 0.128mol), 4, 4, 4', 4', 5, 5, 5', 5'-octamethyl-2, 2'-bi-(1, 3, 2-dioxaborolane) (48.58g, 0.191mol), Pd(dppf)Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol) and a mixture of DMF (500ml), 12 hours with stirring at 130 °C. After completion of the reaction, and extracted with ethyl acetate, to remove water with MgSO4, is purified by Karamukuro Matogurafi (Hexane: EA = 10: 1 (v / v)) was obtained 5-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane-2-yl)-1H-indole (12.43g, 40percent yield).5-bromo-1H-indole (25 g, 0.128 mol) was added under a nitrogen stream, 4, 4, 4 ', 4', 5, 5, 5 ', 5'-octamethyl-2, 2'-bi (1, 3, 2-dioxaborolane)(48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) andWere mixed DMF (500 ml) And the mixture was stirred at 130 DEG C for 12 hours.After the reaction was completed, the reaction mixture was extracted with ethyl acetate, the water was removed with MgSO4, Purification by column chromatography (Hexane: EA = 10: 1 (v / v)) gave5- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H-indole(12.43 g, yield 40percent).To a solution of 5-bromo-1H-indole (200 mg, 1.02 mmol) in dioxane (10 mL) were added bis (pinacolato) diboron (309.8 mg, 1.22 mmol) , potassium acetate (300 mg, 3.06 mmol) , X-Phos (48.5 mg, 0.10 mmol) and tris (dibenzylideneacetone) dipalladium (46.7 mg, 0.05 mmol) . The mixture was stirred under NBromide 1-6-a (3.92 g, 20 mmol), boronic acid pinacol ester (6.22 g, 24 mmol), 1, 1'-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (0.49 g, 0.6 mmol), potassium acetate (5.90 g, 0 mmol) and 79 ml of toluene The reaction was refluxed for 16 hours, cooled, added with 26 ml of water, stirred for 30 minutes, the organic phase was separated, filtered through a short celite bed, and then the organic solvent was evaporated, and the crude product was recrystallized from heptane / toluene; Under argon atmosphere, The obtained solid (3.65 g, 15 mmol), bromobenzene (2.06 g, 14.3 mmol), tetrakis(triphenylphosphine)palladium (0.35 g, 0.3 mmol), toluene (43 ml), aqueous sodium carbonate (2M, 21 ml) The mixture was placed in a flask, and the mixture was refluxed for 8 hours, cooled to room temperature, and extracted with toluene. The organic phase was washed with saturated brine, and then dried, and then purified by column chromatography to afford compound 1-6 3.59 g.

Molecular Weight:243.11
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:243.1430590
Monoisotopic Mass:243.1430590
Topological Polar Surface Area:34.2
Heavy Atom Count:18
Complexity:316
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes