* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Green Chemistry, 2010, vol. 12, # 6, p. 1097 - 1105
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 24, p. 9680 - 9696
3
[ 585-76-2 ]
[ 591-18-4 ]
Yield
Reaction Conditions
Operation in experiment
80%
With N-iodo-succinimide; [4,4’-bis(tert-butyl)-2,2’-bipyridine]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl]iridium(III) hexafluorophosphate; iodine; caesium carbonate In 1,2-dichloro-ethane at 50℃; for 24 h; Inert atmosphere; Irradiation; Sealed tube
General procedure: To a 15 mL test tube with septum Cs2CO3 (0.6 mmol, 195 mg), aromaticcarboxylic acid (1) (0.3 mmol), [Ir(dF(CF3)ppy)2dtbbpy]PF6 (D) (6 μmmol, 6.7 mg), NIS (1.5mmol, 337.5 mg) and I2 (60 μmol, 20 molpercent) were added. The tube was evacuated and backfilledwith argon for three times, and then 3 mL of dry DCE was added through a syringer under argon.The tube was sealed with Parafilm Mr® and placed in an oil bath with a contact thermometer, andthe reaction was carried out at 50 °C under irradiation with 6 × 5 W blue LEDs (λmax = 455 nm).After 24 h or 36 h, the resulting mixture was filtered through a 2 cm thick pad of silica, and thesilica was washed with DCM) (50 mL). The filtrate was collected and the solvent was removed invacuo. The crude residue was purified by silica gel flash column chromatography to provide thetarget product (2). (Note: The reaction was very sensitive to moisture, and the yields sharplydecreased to less than 5percent when 0.01 equivalent of H2O was added to the reaction system).
61%
With 1-iodo-3,5,5-trimethylhydantoin In tetrachloromethane for 15 h; Reflux; Irradiation
[00216] A mixture of 3 -bromobenzoic acid (0.40 g, 2.0 mmol), l-iodo-3,5,5- trimethylhydantoin (0.80 g, 3.0 mmol), and CC (10 mL) was refluxed under irradiation with tungsten lamp for 15 h. The cold reaction mixture was washed with 1 M aq Na2S03 (2 x 5 mL), dried over Na2S04, filtered through short neutral alumina pad and concentrated in vacuo to give 0.35 g (61percent) of 3- bromoiodobenzene. The combine aq sodium sulfite washings were extracted with DCM (3 x 10 mL), carefully acidified with cone, hydrochloric acid to pH 2 and stirred at 0-5 °C for 2 h. The precipitated solid was filtered off, washed on the filter with cold water and dried in vacuo to recover 0.12 g (30percent) of 3- bromobenzoic acid. The combine DCM extracts were dried over Na2S04, filtered and concentrated in vacuo to obtain 0.21 g (75percent) of 3,5,5-trimethylhydantoin.
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
Reference：
[1] Journal of the American Chemical Society, 1982, vol. 104, # 14, p. 3917 - 3923
16
[ 108-86-1 ]
[ 108-95-2 ]
[ 591-18-4 ]
[ 583-55-1 ]
[ 589-87-7 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1987, p. 1167 - 1174
17
[ 626-01-7 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
18
[ 7553-56-2 ]
[ 63467-81-2 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
19
[ 7553-56-2 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
20
[ 7553-56-2 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
21
[ 7553-56-2 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
22
[ 7553-56-2 ]
[ 20893-74-7 ]
[ 591-18-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
23
[ 591-18-4 ]
[ 201230-82-2 ]
[ 22726-00-7 ]
Yield
Reaction Conditions
Operation in experiment
90%
With ammonium hydroxide; 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane; palladium diacetate In toluene at 120℃; for 20 h; Autoclave
General procedure: To a 45 mL glass-lined autoclave, 1 (0.5 mmol), Pd(OAc)2 (0.01mmol), CYTOP®292 (0.02mmol), aqueous ammonia (0.2 mL) and toluene (10 mL) were sequentially added. After sealing, the autoclave was purged three times with carbon monoxide and pressurized with 100 psi of CO. The resulting mixture was then heated at 100 °C for 20 h. The autoclave was removed from the oil bath and cooled to room temperature prior to the release of excess carbon monoxide. The reaction mixture was concentrated by rotary evaporator, and purified by flash chromatography on silica gel with a mixture of hexanes and ethyl acetate (2:1to 1:2) as the eluent to afford the products.
Reference：
[1] Journal of the American Chemical Society, 1982, vol. 104, # 14, p. 3917 - 3923
25
[ 591-18-4 ]
[ 625-99-0 ]
Reference：
[1] Journal of Organic Chemistry, 1993, vol. 58, # 18, p. 4794 - 4795
26
[ 591-18-4 ]
[ 201230-82-2 ]
[ 62-53-3 ]
[ 63710-33-8 ]
Yield
Reaction Conditions
Operation in experiment
100%
With triethylamine In N,N-dimethyl-formamide at 100℃; for 8 h; Schlenk technique; Inert atmosphere
General procedure: In a typical experiment a solution containing the palladiumcatalyst (with 6 mol Pd-content) was placed in a Schlenk-tube.Under argon, 0.2 mmol (22.5 l) iodobenzene (1), 0.5 mmol aminereagent, 0.7 mmol (100 l) triethylamine and 1 ml solvent wasadded and the atmosphere was changed to carbon monoxide. Thereaction mixture was heated with stirring in an oil bath at 100Cand was analysed by gas chromatography.
Reference：
[1] Journal of Molecular Catalysis A: Chemical, 2015, vol. 397, p. 150 - 157
Reference：
[1] Organic Letters, 2017, vol. 19, # 19, p. 5182 - 5185
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 19, p. 4096 - 4114
[3] Chinese Chemical Letters, 2016, vol. 27, # 6, p. 961 - 963
[4] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 630 - 639
[5] Chemistry - A European Journal, 2000, vol. 6, # 13, p. 2362 - 2367
[6] Organic letters, 2002, vol. 4, # 19, p. 3199 - 3202
[7] Journal of Organic Chemistry, 2000, vol. 65, # 18, p. 5712 - 5719
[8] Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1499 - 1503
[9] Organic Letters, 2012, vol. 14, # 4, p. 1106 - 1109
[10] Chemical Communications, 2012, vol. 48, # 30, p. 3617 - 3619
[11] Journal of Organic Chemistry, 2012, vol. 77, # 13, p. 5633 - 5645
[12] Chemistry Letters, 2013, vol. 42, # 10, p. 1128 - 1130
[13] Organic Letters, 2015, vol. 17, # 10, p. 2522 - 2525
[14] Journal of Organic Chemistry, 2018, vol. 83, # 15, p. 8281 - 8291
35
[ 121-43-7 ]
[ 591-18-4 ]
[ 89598-96-9 ]
Yield
Reaction Conditions
Operation in experiment
67.6%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Inert atmosphere Stage #2: at -78 - 20℃;
500ml round bottom flask was placed 1-bromo-3-iodo-benzene (25.0g, 88mmol) was dissolved into 200ml of tetrahydrofuran. The reaction solution was cooled road -78 under a nitrogen atmosphere. A n-butyllithium (60.75ml, 97mmol) to the cooled solution was slowly added dropwise thereto for 30 minutes, the mixture was stirred for 1 hour at the same temperature. Trimethyl borate (11g, 106mmol) were added dropwise at the same temperature the mixture was stirred at room temperature overnight. It was acidified by dropwise addition of 2 normal hydrochloric acid to the reaction solution, which was stirred for 1 hour. Extraction with ethyl acetate was separated organic layer was concentrated under reduced pressure, crystallization was put in a cold n-hexane. Intermediate 11-a> was obtained. (12g, 67.6percent).
67.6%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Inert atmosphere Stage #2: at -78 - 20℃; Inert atmosphere
Insert the 1-bromo-3-iodo-benzene (25.0g, 88mmol) in 500ml round bottom flask was put in a 200ml tetrahydrofuranDissolved.The reaction solution was cooled road -78 under a nitrogen atmosphere.It was slowly added dropwise for 30 minutes n-butyllithium (60.75ml, 97mmol) to the cooled solution,It was stirred for 1 hour at the same temperature.Trimethyl borate (11g, 106mmol) were added dropwise at the same temperature the mixture was stirred at room temperature overnight. It was acidified by dropwise addition of 2 normal hydrochloric acid to the reaction solution, which was stirred for 1 hour. Ethyl acetate was extracted with Tay organic layer was separated and concentrated under reduced pressure, crystallized into the cold n-hexane it was obtained (12g, 67.6percent).
Reference：
[1] Patent: KR2015/130206, 2015, A, . Location in patent: Paragraph 0862-0867
[2] Patent: KR2016/13678, 2016, A, . Location in patent: Paragraph 0324-0330
36
[ 591-18-4 ]
[ 570391-20-7 ]
Reference：
[1] Journal of the American Chemical Society, 2003, vol. 125, # 26, p. 7792 - 7793
[2] Journal of the American Chemical Society, 2015, vol. 137, # 2, p. 592 - 595
37
[ 591-18-4 ]
[ 1692-25-7 ]
[ 4422-32-6 ]
Yield
Reaction Conditions
Operation in experiment
100%
With potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere
1-bromo-3-iodobenzene (1.118 g, 3.95 mol) and 3-pyridine boronic acid (0.559 g, 4.54 mol) were added to a 100 mL three neck round bottom flask. To this flask, dioxane (20 mL) and aqueous K2CO3 (2 N, 20 mL) were added. The mixture was stirred and degassed with a steam of argon for 30 minutes. Then under argon atmosphere, 50 mg (0.04 mmol) of Pd(PPh3)4 (1percent) was added. The mixture was heated to 100° C. and stirred overnight. The next day, the solvent was removed by roto-evaporation and the residue was suspended into an equal amount of water (50 mL) and CH2Cl2 (50 mL). The organic layer was separated from aqueous layer and washed with brine (50 mL.x.3). After drying over Na2SO4, and removal of the drying agent, about 0.92 g of 3-(3-bromophenyl)pyridine product (100percent) was afforded. 1H NMR (400 MHz, CDCl3) 8.85 (s, 1H), 8.65 (d, 1H), 7.87 (d, 1H), 7.75 (s, 1H), 7.57-7.52 (m, 2H), 7.41-7.35 (m, 2H).
88%
With palladium diacetate; sodium carbonate; triphenylphosphine In 1,2-dimethoxyethane; water for 18 h; Inert atmosphere; Reflux
A mixture of 3-bromoiodobenzene (19.8 g, 70.0 mmol, pyridine-3- borononic acid (8.6 g, 70.0 mmol) in 1 ,2-dimethoxyethane (315 mL) and 2.0 M aqueous sodium carbonate (105 mL) was sparged with nitrogen for 30 minutes, then palladium acetate (393 mg, 1 .75 mmol) and triphenylphosphine (918 mg, 3.50 mmol) were added and the mixture was heated at reflux for 18 h. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3 x 150 ml_). The combined organic layer was washed with water and brine (2 x 150 ml_ each), then dried over magnesium sulfate, filtered and concentrated to a dark brown oil. The crude product was purified by silica gel MPLC (0 - 90percent ethyl acetate in hexanes as eluent). The product fractions eluting when the gradient had reached 55 - 85percent ethyl acetate in hexanes were combined and concentrated by rotary evaporation to give 3-(3-bromophenyl)pyridine as a dark yellow oil (14.5 g, 88percent yield) having a purity of 97percent based on UPLC analysis. This material was taken directly to Step 2.
77%
With sodium carbonate In 1,4-dioxane; water at 95℃; for 24 h; Inert atmosphere
Example 14; Synthesis of Compound 31; A 100 mL, round-bottomed Schlenk flask equipped with a magnetic stir bar was charged with 1-bromo-3-iodobenzene (5.754 g, 20.3 mmol), 3-pyridyl boronic acid (2.5 g, 20.3 mmol), 25 mL of a 2 M aqueous solution of Na2CO3, and 25 mL of 1,4-dioxane. Tetrakis (triphenylphosphine) palladium (0.54 g, 0.5 mmol) was added, the mixture was degassed using five vacuum/nitrogen back-fill cycles, and then was heated to 95° C. for 24 hours with vigorous stirring. The reaction mixture was allowed to cool to room temperature and diluted with CH2Cl2. The organic layer was washed with 1N HCl, H2O, and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The resulting yellow solid was purified by column chromatography on silica gel. Eluent ethyl acetate/hexane (3/97) gave compound 31 as a pale yellow oil 3.6 g (77percent). 1H NMR (400 MHz, CDCl3) δ 8.82 (br s, 1H), 8.63 (m, 1H), 7.85 (m, 1H), 7.73 (m, 1H), 7.53 (m, 2H), 7.36 (m, 2H).
46%
With sodium hydrogencarbonate In 1,4-dioxane; water at 90℃; for 24 h;
149] 3-(3-Bromophenyl)pyridine (lib): A solution of pyridine 3-boronic acid 51 (1.0 g, 8.14 mmol), 3-bromo-l-iodobenzene 50 (2.0 g, 7.07 mmol) and sodium bicarbonate (1.5 g, 17.7 mmol) in dioxane (16 niL) and water (4 mL) was purged with N2 for 5 min.Tetrakis(triphenylphosphine)palladium (400 mg, 0.35 mmol) was added and the mixture was heated at 90 0C for 24 hr. The solution was cooled and the volatile organics were evaporated. The residue was partitioned between EtOAc (50 mL) and water and the layers were separated. The organic layer was washed with water, dried (Na2SO4), and concentrated to give 2.2 g of yellow oil. The crude material was purified on an Analogix automated system (24 g column, 0- 30percent EtOAc/heptane) to provide 760 mg (46percent) of pure lib. Some impure material was set aside.
Reference：
[1] Journal of Organic Chemistry, 1999, vol. 64, # 19, p. 6999 - 7008
39
[ 591-18-4 ]
[ 73183-34-3 ]
[ 594823-67-3 ]
Yield
Reaction Conditions
Operation in experiment
69%
With pyridine; cesium fluoride In dimethyl sulfoxide at 105℃; for 2 h; Inert atmosphere; Schlenk technique
General procedure: An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinacolatodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere, freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5mmol), and pyridine (0.4 to 1 equiv) were added successively. The reaction mixture was heated to 105 °C and stirred for 2 h under argon.
Stage #1: at 20 - 40℃; for 3 h; Stage #2: With water; ammonium chloride In diethyl ether; toluene
lsobutylmagnesium bromide (2M in diethyl ether, 26.5ml, 53mmol) was added over 30 minutes at room temperature to a solution of 1-bromo-3-iodobenzene (1Og, 35.3mmol) and tetrakis(triphenylphosphine)palladium (0) (1.1 g, 0.954mmol) in toluene (160ml). The reaction mixture became green and the temperature was not allowed to rise above 400C. The reaction mixture was then stirred at room temperature for three hours. Aqueous ammonium chloride solution (160ml) was then added (the reaction became red) and the mixture was extracted with diethyl ether (2x100ml). The organics were washed with more ammonium chloride (100ml), dried over magnesium sulphate and concentrated under reduced pressure. The crude product was then purified by distillation to provide the title compound (boiling point 88°C under 25mmHg, 3.2Og, 42percent). 1H-NMR (400MHz, CDCI3) : δ = 0.90 (d, 6H), 1.85 (m, 1 H), 2.44 (d, 2H), 7.07 (d, 1 H), 7.14 (t, 1 H)1 7.30 (m, 2H).
With copper; potassium carbonate In N,N-dimethyl-formamide at 130℃;
Carbazole 2.00 g (12.0 mmol), 1-bromo-3-iodobenzene, 2.02 mL (15.8mmol), copper (Cu) 2.29 g (36.0 mmol) of calcium carbonate and 4.98 g (36.0 mmol) of DMF in 30 mL insert heated at 130 It was stirred. After the completion of the reaction, it cooled to ambient temperature and diluted with ethyl acetate to a vacuum filter, and passed through a silica gelThe filtrate was concentrated under reduced pressure. Separating the product by silica gel column chromatography (ethyl acetate: n- hexane = 1: 20) to give the desired intermediate compound (C) 3.80 g (98percent yield).
90%
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃;
In a dry 2L three-necked flask, 42.3 g of m-bromo iodobenzene and 27.5 g of carbazole were added. Then dry and degassed 800 mL of toluene was added as a solvent. Add 43.2g of sodium tert-butoxide (3eq.), 0.67 g of palladium acetate (2percent mol) and 3.7 g of ligand 1, 1′-binaphthyl-2,2′-bisdiphenylphosphine (BINAP, 4percent mol). The temperature was raised to 110°C and the reaction ended overnight. Cool to room temperature Activated carbon adsorption, suction filtration, solvent removal, recrystallization with toluene and ethanol, 40.9 g of intermediate I are obtained (yield 90percent).
89%
With copper; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 24 h; Inert atmosphere
1-bromo-3 - iodo-benzene (145 ml, 53 mmol), carbazole (8.7 g, 52 mmol), copper powder (10.1 g, 159 mmol) and potassium carbonate (22 g, 159 mmol) dimethyl was dissolved in formamide (120 ml), it was stirred under argon for 24 hours in the presence of 130 . When complete the reaction, The reaction mixture was cooled to ambient temperature, filtered on Celite mukhyeo ethyl acetate. Filtered, poured in water, extracted with ethyl acetate, and wash the organic layer extracted with brine. The washed organic layer was dried over magnesium sulfate and purified by column chromatography (silica gel) to give the title compound (14.9 g, 89percent).
82.4%
at 150℃; for 48 h; Inert atmosphere
Synthesis example 3:; Synthesis of N-(3-bromophenyl)carbazole (compound 4); (4) Under nitrogen, carbazole (24.3 g, 1 eq.) is added to a flask together with 1 -bromo-3- iodobenzene (98percent; 75.3 g, 1.9 eq.), potassium carbonate (48.2 g, 2.5 eq.) and copper (1 .77 g, 0.1 eq.). The reaction is heated to 150°C and stirred at 150°C for 48 h. The mixture is cooled to room temperature and diluted with 150 ml. of methylene chloride. 100 mL of demineralized water are added to the mixture, which is stirred. Removal of the aqueous phase is followed by washing a further 2x with demineralized water (100 mL). The organic phase is dried over sodium sulfate and concentrated. The excess 1 -bromo-3-iodobenzene is distilled off under reduced pressure. LC (Si02; cyclohexane/ methylene chloride 95:5) gives 37.1 g of product (82.4percent yield).1H NMR (CD2CI2, 400 MHz): δ = 8.13 (d, 2H), 7.75 (s, 1 H), 7.61 (d, 1 H), 7.53 (d, 1 H), 7.49 (d, 1 H), 7.42 (m, 4H), 7.27-7.31 (m, 2H)
79%
With 18-crown-6 ether; copper; potassium carbonate In N,N-dimethyl-formamide at 150℃; Inert atmosphere
A mixture of 9-H carbazole (4.0 g, 24.1 mmol), 3-bromoiodobenzene (10.23 g, 36.1 mmol), copper (3.06 g, 48.2 mmol), potassium carbonate (13.3 g, 96.4 mmol), 18-crown-6 (636 mg, 2.41 mmol) and DMF (anhydrous, 50 mL) was degassed for about 40 minutes. The mixture was then further degassed by heating to about 150° C. overnight under argon. After cooling to room temperature (RT), solids from reaction mixture were then filtered off. The filtrate was then poured into dichloromethane (DCM) (250 mL) and then washed with water (3×200 mL). The organic layer was dried over sodium sulfate and loaded onto silica gel. A flash column (hexanes) gave 6.56 g (79percent yield) of product 1B; pure by HNMR.
78%
With copper; potassium carbonate In Tetraethylene glycol dimethyl ether at 140℃; for 5 h;
Under nitrogen flow, carbazole (7.00 g), 3-bromoiodobenzene (14.2 g), copper powder (2.66 g), potassium carbonate (5.79 g), and tetraglyme (10 ml) were stirred while heating to 140°C for 5 hr and then allowed to cool to room temperature. After the completion of the reaction, chloroform was added to the reaction solution, and the insoluble matter was removed by filtration. Chloroform contained in the filtrate was evaporated under reduced pressure, and the resulting matter was purified by silica-gel column chromatography (n-hexane/toluene = 4/1) and dried under reduced pressure to obtain a target compound 11 (10.5 g, yield: 78percent) as a colorless viscous liquid.
78%
With copper(l) iodide; potassium carbonate In 5,5-dimethyl-1,3-cyclohexadiene for 48 h; Inert atmosphere; Reflux
In the reaction flask carbazole 3.0g, meta-bromoiodobenzene 10.15g, 2.39 g copper iodide, 4.95g of potassium carbonate and 40mL of dry xylene, the reaction was refluxed for 48 hours nitrogen, was added 50mL of water quench off the reaction, extracted with dichloromethane, the solvent was evaporated, purified by column chromatography to give a white colored final precipitate 9-(3-bromophenyl)-9H- carbazole 3.5g, 78percent yield.
70%
With potassium phosphate; copper(l) iodide In 1,4-dioxane at 90℃; for 12 h; Inert atmosphere
Under a nitrogen atmosphere (N2 purging), Compound 1G(10 g, 35.48 mmol), 0.6 equivalent of Compound 1H, 0.1 equivalent of CuI, 3.5 equivalents of diaminocyclohexane, and 4.0 equivalents of potassium phosphate were added to 1,4-dioxane(350 ml), and stirred in a 90° C. oil bath. After 12 hours, water was added to the reaction mixture, and extraction was performed. Then, purification was performed using a column using a developing solvent of MC:hexane (5:1) to obtain a white solid 11(7.97 g, yield 70percent).
69%
With potassium phosphate; copper(II) iodide; rac-diaminocyclohexane In 1,4-dioxane for 16 h; Inert atmosphere; Reflux
In 250mL three-necked flask, were added carbazole 16.72g, m-bromoiodobenzene 42.44g, cuprous iodide 1.9g, 1,2- diaminocyclohexane 3.42g, 42.4g anhydrous potassium phosphate and solvent 1 , 4-dioxane 160mL, N2 replaced three times, heated to reflux and the reaction stopped after 16h.Cooled to room temperature, filtered, and the filtrate was collected, purified by column chromatography (dichloromethane: n-hexane = 1: 1-1: 0), the target receives the solid product 22g (69percent).
35%
With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 100℃; for 16 h; Inert atmosphere; Reflux
Sigma aldrich in nitrogen (http://www. Sigmaaldrich. Com /) carbazole yarn (50 g, 299. 0 mmol) of toluene 0. 5 L senses a rotation velocity of the disk to, herein 1-bromo-3-iodobenzene sigma aldrich yarn (101. 5 g, 358. 8 mmol), bis (dibenzylideneacetone) palladium (0) (5. 16 g, 8. 97 mmol), tris-tert butylphosphine (3. 02 g, 15. 0 mmol) and sodium tert-butoxide (34. 5 g, 358. 8 mmol) in 100 °C sequentially and at the reflux by heating at a 16. Complete after reaction solution at a water doesn't have any error frames, then dichloromethane (DCM) extraction of water to the MgSO4 anhydride after triggers number, filter and was, concentrating it under reduced pressure. Thus-obtained residue number intermediate that is forward separated into flash column chromatography I-2 (33. 3 g, 35percent) a obtained
1.9 g
Stage #1: With tri-tert-butyl phosphine; palladium diacetate In toluene at 20℃; for 1 h; Inert atmosphere Stage #2: at 80℃; for 6 h; Inert atmosphere
250ml 3-neck round bottom flask was charged 1-3 (5g), palladium(0)diacetate (0.1g), tri-tert-butylphosphine (0.3g), put the toluene (100ml), 1 h on the atmosphere of argon at room temperature It was stirred. After the addition of potassium carbonate (7.2g), 3- bromo carbazole (6.3g) in the mixture was stirred at 80 °C for 6 hours. After the addition of water and extracted with ethyl acetate to give 1.9g the title 1-4 substituents through a separation column using hexane and the resulting material after removal of water.
Reference：
[1] Patent: KR101593182, 2016, B1, . Location in patent: Paragraph 0427; 0430; 0438; 0439
[2] Patent: CN107686484, 2018, A, . Location in patent: Paragraph 0123-0128
[3] Patent: KR101622443, 2016, B1, . Location in patent: Paragraph 0109; 0110
[4] RSC Advances, 2015, vol. 5, # 64, p. 51512 - 51523
[5] Patent: WO2012/4765, 2012, A2, . Location in patent: Page/Page column 73-74
[6] Patent: US2013/75706, 2013, A1, . Location in patent: Paragraph 0074
[7] Patent: EP1820801, 2007, A1, . Location in patent: Page/Page column 82; 83
[8] Patent: CN103588770, 2016, B, . Location in patent: Paragraph 0046
[9] Organic Electronics: physics, materials, applications, 2011, vol. 12, # 6, p. 1025 - 1032
[10] Patent: US2018/166636, 2018, A1, . Location in patent: Paragraph 0119; 0120
[11] Patent: CN103951621, 2016, B, . Location in patent: Paragraph 0072; 0073; 0075; 0076
[12] Journal of Materials Chemistry C, 2014, vol. 2, # 31, p. 6333 - 6341
[13] RSC Advances, 2015, vol. 5, # 22, p. 17030 - 17033
[14] Patent: KR2016/91198, 2016, A, . Location in patent: Paragraph 0212
[15] Patent: US2010/187984, 2010, A1, . Location in patent: Page/Page column 121
[16] Chemistry of Materials, 2011, vol. 23, # 2, p. 274 - 284
[17] Advanced Materials, 2011, vol. 23, # 12, p. 1436 - 1441
[18] Journal of Materials Chemistry, 2012, vol. 22, # 15, p. 7239 - 7244
[19] Journal of Materials Chemistry, 2012, vol. 22, # 8, p. 3447 - 3456
[20] Patent: US2013/119367, 2013, A1, . Location in patent: Page/Page column
[21] Patent: WO2016/102413, 2016, A1, . Location in patent: Paragraph 0080
[22] Patent: KR2015/136713, 2015, A, . Location in patent: Paragraph 0081-0087
[23] Patent: WO2016/102414, 2016, A1, . Location in patent: Paragraph 0068
[24] Patent: JP5856161, 2016, B2, . Location in patent: Paragraph 0054
44
[ 591-18-4 ]
[ 185112-61-2 ]
Yield
Reaction Conditions
Operation in experiment
82.4%
With copper; potassium carbonate In dichloromethane; water
Synthesis Example 3 Synthesis of N-(3-bromophenyl)carbazole (compound 4) Under nitrogen, carbazole (24.3 g, 1 eq.) is added to a flask together with 1-bromo-3-iodobenzene (98percent; 75.3 g, 1.9 eq.), potassium carbonate (48.2 g, 2.5 eq.) and copper (1.77 g, 0.1 eq.). The reaction is heated to 150° C. and stirred at 150° C. for 48 h. The mixture is cooled to room temperature and diluted with 150 mL of methylene chloride. 100 mL of demineralized water are added to the mixture, which is stirred. Removal of the aqueous phase is followed by washing a further 2* with demineralized water (100 mL). The organic phase is dried over sodium sulfate and concentrated. The excess 1-bromo-3-iodobenzene is distilled off under reduced pressure. LC (SiO2; cyclohexane/methylene chloride 95:5) gives 37.1 g of product (82.4percent yield). 1H NMR (CD2Cl2, 400 MHz): δ=8.13 (d, 2H), 7.75 (s, 1H), 7.61 (d, 1H), 7.53 (d, 1H), 7.49 (d, 1H), 7.42 (m, 4H), 7.27-7.31 (m, 2H)
Reference：
[1] Patent: US2012/7063, 2012, A1,
45
[ 591-18-4 ]
[ 32316-92-0 ]
[ 667940-23-0 ]
Yield
Reaction Conditions
Operation in experiment
85%
With potassium carbonate In tetrahydrofuran for 24 h; Heating / reflux
2- A. Production of compound 2a; [79] After l-bromo-3-iodobenzene (10 g, 35.35 mmol) and 2-naphthalene bromic acid(5.47 g, 31.82 mmol) were dissolved in anhydrous THF (100 mL), Pd(PPh ) (1.2 g, 1.06 mmol) and 50 mL of 2M K CO aqueous solution were added and then refluxed <n="17"/>for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2a (8.5 g, 85percent).[80] MS [M + H] = 283
76%
With sodium carbonate In water; toluene for 24 h; Inert atmosphere; Reflux
Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthaleneboronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine)palladium(0), 6.4 L of toluene and 3.2 L of aqueous solution of 2M sodium carbonate were added together, and stirred while being refluxed for 24 hours. After the reaction was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was washed by water and dried with magnesium sulfate, the toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2-(3-bromophenyl)naphthalene was obtained at an yield of 76percent.
Reference：
[1] Patent: WO2008/13399, 2008, A1, . Location in patent: Page/Page column 14-15
[2] Patent: US2010/331585, 2010, A1, . Location in patent: Page/Page column 94-95
[3] Organic and Biomolecular Chemistry, 2017, vol. 15, # 19, p. 4096 - 4114
46
[ 1694-31-1 ]
[ 591-18-4 ]
[ 197792-52-2 ]
Yield
Reaction Conditions
Operation in experiment
84%
With 2-Picolinic acid; copper(l) iodide; caesium carbonate In 1,4-dioxane at 70℃; Inert atmosphere
General procedure: General procedure for the synthesis of α-arylacetic acid tert-butyl esters: A Schlenk tube was charged with aryl iodide (1.0mmol), CuI (9.5mg, 0.05mmol), 2-picolinic acid (12mg, 0.10mmol), and cesium carbonate (978mg, 3.0mmol). The tube was evacuated and backfilled with argon three times before tert-butyl acetoacetate (2.0mmol) and 2mL of 1,4-dioxane was added. The tube was immersed in an oil bath, and the reaction mixture was stirred at the indicated temperatures for 33–48h. The cooled mixture was partitioned between ethyl acetate and saturated NH4Cl, the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with PE/EA=20:1 to 3:1) to provide the desired α-arylacetic acid tert-butyl esters.
Reference：
[1] Patent: EP2947071, 2015, A1,
[2] Patent: KR2016/11036, 2016, A,
[3] Patent: JP2016/88927, 2016, A,
[4] Patent: KR2016/19747, 2016, A,
[5] Patent: KR2015/135070, 2015, A,
[6] Patent: US2018/94000, 2018, A1,
52
[ 288-13-1 ]
[ 591-18-4 ]
[ 294877-33-1 ]
Yield
Reaction Conditions
Operation in experiment
78%
With potassium phosphate monohydrate; manganese(II) chloride tetrahydrate; (S,S)-1,2-diaminocyclohexane In water for 24 h; Reflux
In a 500 ml round-bottomed flask, 10.0 g (147 mmol) pyrazole,2.91 g (14.7 mmol) of MnCl 2 .4H 2 O, 67.7 g (294 mmol) of K 3 PO 4 .H 2 O,62.3 g (220 mmol) of 1-bromo-3-iodobenzene, 3.35 g (29.4 mmol) of trans-1,2-diaminocyclohexane and 70 ml of water were added and refluxed for 24 hours.After completion of the reaction, the temperature was lowered to room temperature, and methylene chloride was added thereto, followed by filtration using Celite.The filtrate was concentrated under reduced pressure and then subjected to column purification using ethyl acetate and n-hexane as eluent. (25.6 g, yield 78percent).
51%
With copper(l) iodide; (S,S)-1,2-diaminocyclohexane; potassium carbonate In 1,4-dioxane for 19 h; Reflux
1-bromo-3-iodobenzene (18.20 g, 64.3 mmol), 1H-pyrazole (4.38 g, 64.3 mmol), and (1S,2S)-cyclohexane-1,2-diamine (1.5 g, 12.9 mmol) in dioxane (400 mL) were placed into a 1 L round-bottomed flask. Copper(I) iodide (0.613 g, 3.22 mmol) and potassium carbonate (17.78 g, 129 mmol) were added, and the reaction mixture was stirred at reflux for 19 h. The crude mixture was then filtered through a pad of celite. The filtrate was diluted with 400 mL of dichloromethane, and was washed with water. The organic layer was concentrated and chromatographed on silica gel with 5percent ethyl acetate in hexane to give 7.3 g (51percent) of 1-(3-bromophenyl)-1H-pyrazole as a white solid. Synthesis of N-(3-(1N-pyrazol-1-yl)phenyl)-3-(1-(2,6-dimethylphenyl)-1H-imidazol-4-yl)-N-phenylaniline.
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Inert atmosphere Stage #2: at 20℃; for 1.5 h; Inert atmosphere
To a round bottom flask, 1-bromo-3-iodo-benzene (60.0 g, 212 mmol), 480 mL of tetrahydrofuran were added and the temperature falls to -78° C under a nitrogen condition . After 30 minutes, 126 mL of 1.6 M n-butyllithium (202 mmol) was slowly added dropwise . After 1 hour, 2-chloro-4,6-diphenyl-1,3,5-triazine 62.4 g (233 mmol) was dissolved in 250 mL of tetrahydrofuran, after dropping a solution slowly comes to room temperature and then stirred for 30 minutes. After stirring for about 1 hour at room temperature, 2N hydrochloric acid was added dropwise to the reaction solution until the acid is an aqueous solution. The combined organic layer was then extracted, concentrated and then separated by column chromatography to give <4-a> 24.7g (yield 30percent).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 10 h; Inert atmosphere; Reflux
To a 1000 ml flask was added 30.0 g (83.51 mmol) of Intermediate L-1, 28.35 g (100.21 mmol) of 1-bromo-3-iodebenzene, 23.08 g (167.02 mmol) of potassium carbonate, Tetrakis (triphenylphosphine) palladium )) 4.83 g (4.18 mmol) in tetrahydrofuran(350 mL) and water (100 mL), and the mixture was heated under reflux in a nitrogen stream for 10 hours. The resultant mixture was added to 1500 mL of methanol and the crystallized solid was filtered, and then dichloromethane was added thereto. The resulting mixture was filtered through silica gel / celite, and the organic solvent was removed in an appropriate amount, and the filtrate was recrystallized from methanol to obtain 37.3 g of 83percent Yield).
Reference：
[1] Patent: KR2016/121282, 2016, A, . Location in patent: Paragraph 0127-0131
55
[ 591-18-4 ]
[ 1268954-77-3 ]
Reference：
[1] Patent: EP2471772, 2012, A1,
56
[ 591-18-4 ]
[ 1036378-83-2 ]
[ 1233200-57-1 ]
Yield
Reaction Conditions
Operation in experiment
77%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 80℃; for 12 h; Inert atmosphere
Nitrogen environment in the compound I-8 (50 g, 140 mmol) and tetrahydrofuran (THF) 0.45 L dissolved after, here in 1-bromo-3-iodobenzene (43.7 g, 154 mmol) and tetrakis (triphenylphosphine) palladium (1.62 g and stirred into a 1.40 mmol). Into the potassuim carbonate (48.4 g, 350 mmol) in saturated water it was heated to reflux at 80 for 12 hours. After the reaction was completed, the reaction solution into water and extracted with dichloromethane (DCM), and then removing water by anhydrous MgSO4 One was then filter, and concentrate under reduced pressure. The obtained residue was purified by flash column chromatography to give the compound I-15 (41.5 g, 77percent).
77%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 10 h; Reflux; Inert atmosphere
196.48 mmol) of Intermediate L-5, 72.26 g (255.42 mmol) of 1-bromo-3-iodebenzene, 54.31 g (392.96 mmol) of potassium carbonate, Pd (PPh3) ) Was added to 400 mL of tetrahydrofuran and 200 mL of water, and the mixture was heated under reflux for 10 hours under a nitrogen stream. The resulting mixture was added to 1500 mL of methanol, and the crystallized solid was filtered, and then dichloromethane was dissolved. The mixture was filtered through silica gel / celite, and an organic solvent was removed in an appropriate amount. The residue was recrystallized from methanol to obtain 3-bromo-5'-phenyl The yield of compound 3-bromo-5'-phenyl-1,1 ': 3,1 "-terphenyl (58.63 g, 77percent The results of the analysis are as follows.
Reference：
[1] Patent: KR2015/117173, 2015, A, . Location in patent: Paragraph 0239-0241
[2] Patent: KR2016/19747, 2016, A, . Location in patent: Paragraph 0234-0237
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 24h;Heating / reflux;
2- A. Production of compound 2a; [79] After l-bromo-3-iodobenzene (10 g, 35.35 mmol) and 2-naphthalene bromic acid(5.47 g, 31.82 mmol) were dissolved in anhydrous THF (100 mL), Pd(PPh ) (1.2 g, 1.06 mmol) and 50 mL of 2M K CO aqueous solution were added and then refluxed <n="17"/>for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2a (8.5 g, 85%).[80] MS [M + H] = 283
76%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 24h;Inert atmosphere; Reflux;
Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthaleneboronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine)palladium(0), 6.4 L of toluene and 3.2 L of aqueous solution of 2M sodium carbonate were added together, and stirred while being refluxed for 24 hours. After the reaction was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was washed by water and dried with magnesium sulfate, the toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2-(3-bromophenyl)naphthalene was obtained at an yield of 76%.
Example 202 2,6-Difluoro-N-[3-(3-{5-fluoro-2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-d]pyridin-2-yl)phenyl]benzamide Step A: 1-Bromo-3-ethynylbenzene; To an oven-dried flask under N2 was added 1-bromo-3-iodobenzene (5.00 g, 17.73 mmol), anhydrous, degassed THF (100 mL), dichlorobis(triphenyl-phosphine)palladium(II) (620 mg, 0.88 mmol), copper(I) iodide (100 mg, 0.53 mmol), TEA (7.15 g, 71 mmol), and TMS acetylene (1.91 g, 20 mmol). After stirring overnight at rt, the reaction was washed with brine (100 mL), organic layer separated, concentrated under reduced pressure, adsorbed to silica gel and purified by column chromatography (5% EtOAc in hexanes) to afford the desired product (3.57 g, 80%) as a clear oil. This was dissolved in 100 ml 1:1 THF:MeOH and to this was added water (10 mL), and K2CO3 (5.87 g, 43 mmol). After stirring overnight at rt, the reaction was washed with brine (100 mL), adsorbed to silica gel and purified by LC (5% EtOAc in hexanes) to afford the alkyne (1.92 g, 75%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) delta 3.10 (s, 1H), 7.17 (t, J=7.69 Hz, 1H), 7.38-7.44 (m, 1H), 7.45-7.48 (m, 1H), 7.61-7.62 (s, 1H).
With potassium carbonate; In methanol; acetonitrile; at 40℃;
General procedure: 4-Iodoanisole (1mmol), TMSA (1.1mmol) and K2CO3 (2mmol) were added to a freshly prepared solution of PdNPs (5mL) in a 25mL round bottomed flask fitted with stopper. Then, the reaction mixture was stirred at 40C. The reaction progress was monitored by TLC, until complete consumption of aryl iodide. To the reaction mixture containing in situ formed 4-ethynylanisole the next batch of aryliodide (1mmol) was added and the reaction mixture was further allowed to stir until complete consumption of the arylacetylene. In this manner the targeted unsymmetrical diarylacetylene was formed. The detailed procedure is provided in the Supp. Info. Detailed procedure for synthesis of symmetrical diarylacetylenes is also mentioned in SI.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 12h;Reflux; Inert atmosphere;
(5) Synthesis of Compound (1-e) [0192] [0193] Into a three-necked flask, 12.0 g (59.8 mmol) of 3-bromophenylboronic acid, 25.3 g (89.6 mmol) of 3-bromoiodobenzene, 90 ml of a 2 M aqueous solution of sodium carbonate, 180 ml of 1,2-dimethoxyethane, and 1.38 g (1.20 mmol) of Pd(PPh3)4 were charged, and the contents were refluxed for 12 h in a nitrogen atmosphere. [0194] After the reaction, the reaction solution was extracted with several portions of dichloromethane in a separatory funnel. The extract was dried over anhydrous magnesium sulfate, filtered, and concentrated. The concentrate was purified by silica gel chromatography (hexane), to obtain a white solid. [0195] The yield was 11.2 g and the percent yield was 60%.
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 100 - 110℃; for 5h;Inert atmosphere; Sealed tube;
Step 2. N-(3-Bromophenyl)-4-t-butyl-2-nitroaniline (40): To a sealed tube was added 39 (6 g, 30 mmol), 3-bromoiodobenzene (11.2 g, 40 mmol), Xantphos (0.52 g, 0.9 mmol), sodium tert-butoxide (4.4 g, 46 mmol) and toluene (90 mL). The mixture was purged with nitrogen for 5 minutes then tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.28 g, 0.3 mmol) was added. The tube was sealed and heated at 100-110 C for 5 hours. The reaction was cooled and combined with a 2 g scale front run. The mixture was filtered through a pad of Celite, washing with EtOAc (100 mL). The filtrate was adsorbed onto silica gel and dry- loaded onto a silica gel column eluting with 0-1 :6 EtO Ac/heptanes to give 13 g (92%) of40 as a red solid.
With potassium carbonate;
EXAMPLE 6 3'-Bromo-4-t-butyl-2-nitrodiphenylamine (6d). 4-t-Butyl-2-nitroaniline (see Example 7) (2g, 10.31mmol), 3-bromo-1-iodobenzene (5.84g, 20.62mmol), potassium carbonate (1.52g, 11mmol) and Cu-bronze (20mg) were thoroughly mixed and heated to 160C overnight. After cooling the reaction mixture was partitioned between water and toluene. The organic phase was dried with MgSO4 and evaporated. The remanence was passed through a silica gel column with ethyl acetate/petroleum ether (1:9) as the eluent to yield 6d(2.27g, 61%). Mp 86-87C.
With potassium carbonate;
EXAMPLE 6 3'-Bromo-4-t-butyl-2-nitrodiphenylamine (6d). 4-t-Butyl-2-nitroaniline (see Example 7) (2 g, 10.31 mmol), 3-bromo-1-iodobenzene (5.84 g, 20.62 mmol), potassium carbonate (1.52 g, 11 mmol) and Cu-bronze (20 mg) were thoroughly mixed and heated to 160 C. overnight. After cooling the reaction mixture was partitioned between water and toluene. The organic phase was dried with MgSO4 and evaporated. The remanence was passed through a silica gel column with ethyl acetate/petroleum ether (1:9) as the eluent to yield 6d (2.27 g, 61%). Mp 86-87 C.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux;
Compound 3-biphenylboronic acid (1.98 g, 10 mmol), 1-bromo-3-iodobenzene (2.83 g, 10 mmol), a 2 M aqueous solution of Na2CO3 (10 mL, 20 mmol), toluene (40 mL), and Pd[PPh3]4 (0.35 g, 0.30 mmol) were loaded into a three-necked flask, and the mixture was refluxed under an Ar atmosphere for 10 hours. After the completion of the reaction, the resultant was cooled to room temperature. The resultant sample was transferred to a separating funnel, and water (500 mL) was charged into the funnel. Then, the mixture was extracted with toluene. The extract was dried with MgSO4, and was then filtered and concentrated. The resultant sample was purified by silica gel column chromatography. The purified product was concentrated to dryness, whereby a colorless oily product was obtained in an amount of 2.9 g in 93percent yield. FD-MS analysis C18H13Br: theoretical value 309, observed value 309
91%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 6h;Inert atmosphere;
Nitrogen environment at biphenyl-3-ylboronic acid (100 g, 505 mmol) and tetrahydrofuran (THF) 1.4 L dissolved after, here in 1-bromo-3-iodobenzene (171 g, 606 mmol) and tetrakis (triphenylphosphine) palladium ( 5.83 g, was stirred into a 5.05 mmol). Into the potassuim carbonate (186 g, 1,26 mmol) in saturated water it was heated to reflux at 80 for 6 hours. After the reaction was completed, the reaction solution into water and extracted with dichloromethane (DCM) and then water was removed with anhydrous MgSO4, filter and was concentrated under reduced pressure. The obtained residue was purified by flash column chromatography to give the Intermediate I-1 (142 g, 91percent).
90%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 8h;Inert atmosphere;
100 g (505 mmol) of biphenyl-3-ylboronic acid was dissolved in 1.4 L of tetrahydrofuran (THF) under a nitrogen environment, 171 g (606 mmol) of 1-bromo-3-iodobenzene and 5.84 g (5.05 mmol) of tetrakis(triphenylphosphine)palladium were added thereto, and the mixture was agitated. 174 g (1,263 mmol) of potassium carbonate saturated in water was added thereto, and the resulting mixture was heated and refluxed at 80° C for 8 hours. When the reaction was terminated, water was added to the reaction solution, and the mixture was extracted with dichloromethane (DCM), treated with anhydrous MgSO4 to remove moisture and then, filtered and concentrated under a reduced pressure. The obtained residue was separated and purified through flash column chromatography, obtaining 141 g of an intermediate I-4 (a yield: 90 percent). (0102) HRMS (70 eV, EI+): m/z calcd for C18H13Br: 308.0201, found: 308. (0103) Elemental Analysis: C, 70 percent; H, 4 percent
71%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 10h;Inert atmosphere; Reflux;
(252.49 mmol) of intermediate [1,1'-biphenyl] -3-ylboronic acid, 92.86 g (328.23 mmol) of 1-bromo-3-iodobenzene, 69.79 g (504.97 mmol) of potassium carbonate, Pd(PPh3)4 (Tetrakis(triphenylphosphine)palladium(0)) 14.59 g (12.62 mmol) were placed in 500 mL of tetrahydrofuran and 250 mL of water, and the mixture was heated under reflux under heating in a nitrogen stream for 10 hours. The resulting mixture was added to 1500 mL of methanol, and the crystallized solid was filtered. The filtrate was washed with dichloromethane and silica gel / celite. An organic solvent was removed in an appropriate amount, and the residue was recrystallized from methanol to obtain Compound A-1 (55.32 g, 71 percent Yield). The resulting compound 3-bromo-1,1 ': 3,1'-terphenyl was analyzed as follows.
57.3%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 74℃; for 3h;Inert atmosphere;
1-Bromo-3-iodobenzene (42.44 g, 150 mmol, 1.0 eq.), biphenyl-3-ylboronic acid (29.70 g, 1.0 eq.), sodium carbonate (31.80 g, 2.0 eq.), and tetrakis(triphenylphosphine) palladium(0) (3.47 g, 0.02 eq.) were weighed and put into a 1 L three-necked round bottom flask. Degassing under reduced pressure and nitrogen purge were sufficiently performed. Thereafter, toluene (360 mL), ethanol (90 mL), and water (90 mL) were added thereto in a nitrogen atmosphere, and the mixture was refluxed and stirred at 74° C. After three hours, heating was stopped, and the temperature of the reaction liquid was returned to room temperature. Extraction was performed with toluene three times, the organic solvent layers were then unified, anhydrous sodium sulfate was added thereto, and the mixture was allowed to stand for a while. Sodium sulfate was filtered off, and the solution was concentrated under reduced pressure. The resulting oil was caused to pass through a silica gel short column chromatography using toluene as an eluent, and a fraction containing a desired product was collected and concentrated under reduced pressure. The resulting oil was caused to pass through a silica gel short column chromatography using heptane as an eluent, and a fraction containing a desired product was collected and concentrated under reduced pressure. A desired product ? P3Br? was obtained as a transparent oil (yield: 26.60 g, yield: 57.3percent).
50%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 4h;Inert atmosphere;
A 200-mL round bottom flask equipped with a magnetic stirrer, a condenser and a nitrogen inloutlet adapter was charged with 1-bromo-3-iodobenzene (2.85 g, 10.1 mmol), 3- biphenylboronic acid (1.0 g, 5.05 mmol), water/dioxane (10 mL/40 ml), K2C03 (1.4 g, 10 mmol). The resulting solution was degassed for 5 minutes, then Pd(PPh3)4 (192 mg, 0.25 mmol) was added. The reaction mixture was heated to 80 °C for 4 hours. After being allowed to cool to room temperature, the reaction mixture was diluted with EtOAc (100 mL) and washed with saturated NaHCO3 (40 mL), then brine (40 mL) and dried over Na2SO4. The organic layer was concentrated under reduced pressure and purified on silica gel. Elution with hexane afforded the title compound (782 mg, 50percent) colorless oil. 1H NMR (CDC13, 300 MHz) 7.76- 7.80 (m, 2H), 7.3 1-7.67 (m, 11H).
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 74℃; for 3h;Inert atmosphere;
1- bromo-3-iodobenzene 42.44g (150mmol, 1.0eq.), Biphenyl-3-boronic acid 29.70g (1.0eq.), Sodium carbonate 31.80g (2.0eq .), and tetrakis (triphenylphosphine) palladium (0) 3.47g (0.02eq.) were weighed into 1L three-necked round bottom flask, after sufficient deaeration under reduced pressure and purged with nitrogen under a nitrogen atmosphere in toluene 360mL, the ethanol 90mL and water 90mL was added, followed by reflux and stirring at 74 .After 3 hours, stopped heating, the reaction mixture was returned to room temperature.After extraction three times with toluene, the combined organic solvent layer, anhydrous sodium sulfate was added and left for a while.Filtration of the sodium sulphate, the solution was concentrated under reduced pressure.The resulting oil using toluene as eluent leads to a silica gel short column chromatography and recovered and concentrated under reduced pressure The fractions containing the desired product.The resulting oil with heptane as eluent leads to silica gel column chromatography, were collected, concentrated under reduced pressure The fractions containing the desired product.Target product "P3Br" was obtained as a clear oil (Yield: 26.60g, yield: 57.3percent).
lsobutylmagnesium bromide (2M in diethyl ether, 26.5ml, 53mmol) was added over 30 minutes at room temperature to a solution of 1-bromo-3-iodobenzene (1Og, 35.3mmol) and tetrakis(triphenylphosphine)palladium (0) (1.1 g, 0.954mmol) in toluene (160ml). The reaction mixture became green and the temperature was not allowed to rise above 400C. The reaction mixture was then stirred at room temperature for three hours. Aqueous ammonium chloride solution (160ml) was then added (the reaction became red) and the mixture was extracted with diethyl ether (2x100ml). The organics were washed with more ammonium chloride (100ml), dried over magnesium sulphate and concentrated under reduced pressure. The crude product was then purified by distillation to provide the title compound (boiling point 88C under 25mmHg, 3.2Og, 42%). 1H-NMR (400MHz, CDCI3) : delta = 0.90 (d, 6H), 1.85 (m, 1 H), 2.44 (d, 2H), 7.07 (d, 1 H), 7.14 (t, 1 H)1 7.30 (m, 2H).
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 130℃;
Carbazole 2.00 g (12.0 mmol), 1-bromo-3-iodobenzene, 2.02 mL (15.8mmol), copper (Cu) 2.29 g (36.0 mmol) of calcium carbonate and 4.98 g (36.0 mmol) of DMF in 30 mL insert heated at 130 It was stirred. After the completion of the reaction, it cooled to ambient temperature and diluted with ethyl acetate to a vacuum filter, and passed through a silica gelThe filtrate was concentrated under reduced pressure. Separating the product by silica gel column chromatography (ethyl acetate: n- hexane = 1: 20) to give the desired intermediate compound (C) 3.80 g (98% yield).
96%
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In toluene; for 4h;
Carbazole (Carbazole) (40 g, 1 eq), 1-Bromo-3-iodobenzene (1-bromo-3-iodobenzene) (70 g, 1.5 eq), CuI (6.3 g, 0.2 eq), K3PO4 (70 g, 2 eq), Trans-1,2-cyclohexadianamine (trans-1,2-cyclohexanediamine) (19 g, 1 eq), toluene (toluene) (600 ml) Is placed in a round bottom flask (1-neck-R.B.F.) and stirred. (4h) .Only MC was filtered and the column was separated to obtain a compound P3. (65 g, Step yield = 96%)
90%
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 110℃;
In a dry 2L three-necked flask, 42.3 g of m-bromo iodobenzene and 27.5 g of carbazole were added. Then dry and degassed 800 mL of toluene was added as a solvent. Add 43.2g of sodium tert-butoxide (3eq.), 0.67 g of palladium acetate (2% mol) and 3.7 g of ligand 1, 1?-binaphthyl-2,2?-bisdiphenylphosphine (BINAP, 4% mol). The temperature was raised to 110C and the reaction ended overnight. Cool to room temperature Activated carbon adsorption, suction filtration, solvent removal, recrystallization with toluene and ethanol, 40.9 g of intermediate I are obtained (yield 90%).
89%
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 24h;Inert atmosphere;
1-bromo-3 - iodo-benzene (145 ml, 53 mmol), carbazole (8.7 g, 52 mmol), copper powder (10.1 g, 159 mmol) and potassium carbonate (22 g, 159 mmol) dimethyl was dissolved in formamide (120 ml), it was stirred under argon for 24 hours in the presence of 130 . When complete the reaction, The reaction mixture was cooled to ambient temperature, filtered on Celite mukhyeo ethyl acetate. Filtered, poured in water, extracted with ethyl acetate, and wash the organic layer extracted with brine. The washed organic layer was dried over magnesium sulfate and purified by column chromatography (silica gel) to give the title compound (14.9 g, 89%).
82.4%
With copper; potassium carbonate; at 150℃; for 48h;Inert atmosphere;
Synthesis example 3:; Synthesis of N-(3-bromophenyl)carbazole (compound 4); (4) Under nitrogen, carbazole (24.3 g, 1 eq.) is added to a flask together with 1 -bromo-3- iodobenzene (98%; 75.3 g, 1.9 eq.), potassium carbonate (48.2 g, 2.5 eq.) and copper (1 .77 g, 0.1 eq.). The reaction is heated to 150C and stirred at 150C for 48 h. The mixture is cooled to room temperature and diluted with 150 ml. of methylene chloride. 100 mL of demineralized water are added to the mixture, which is stirred. Removal of the aqueous phase is followed by washing a further 2x with demineralized water (100 mL). The organic phase is dried over sodium sulfate and concentrated. The excess 1 -bromo-3-iodobenzene is distilled off under reduced pressure. LC (Si02; cyclohexane/ methylene chloride 95:5) gives 37.1 g of product (82.4% yield).1H NMR (CD2CI2, 400 MHz): delta = 8.13 (d, 2H), 7.75 (s, 1 H), 7.61 (d, 1 H), 7.53 (d, 1 H), 7.49 (d, 1 H), 7.42 (m, 4H), 7.27-7.31 (m, 2H)
79%
With 18-crown-6 ether; copper; potassium carbonate; In N,N-dimethyl-formamide; at 150℃;Inert atmosphere;
A mixture of 9-H carbazole (4.0 g, 24.1 mmol), 3-bromoiodobenzene (10.23 g, 36.1 mmol), copper (3.06 g, 48.2 mmol), potassium carbonate (13.3 g, 96.4 mmol), 18-crown-6 (636 mg, 2.41 mmol) and DMF (anhydrous, 50 mL) was degassed for about 40 minutes. The mixture was then further degassed by heating to about 150 C. overnight under argon. After cooling to room temperature (RT), solids from reaction mixture were then filtered off. The filtrate was then poured into dichloromethane (DCM) (250 mL) and then washed with water (3×200 mL). The organic layer was dried over sodium sulfate and loaded onto silica gel. A flash column (hexanes) gave 6.56 g (79% yield) of product 1B; pure by HNMR.
78%
With copper; potassium carbonate; In Tetraethylene glycol dimethyl ether; at 140℃; for 5h;
Under nitrogen flow, carbazole (7.00 g), 3-bromoiodobenzene (14.2 g), copper powder (2.66 g), potassium carbonate (5.79 g), and tetraglyme (10 ml) were stirred while heating to 140C for 5 hr and then allowed to cool to room temperature. After the completion of the reaction, chloroform was added to the reaction solution, and the insoluble matter was removed by filtration. Chloroform contained in the filtrate was evaporated under reduced pressure, and the resulting matter was purified by silica-gel column chromatography (n-hexane/toluene = 4/1) and dried under reduced pressure to obtain a target compound 11 (10.5 g, yield: 78%) as a colorless viscous liquid.
78%
With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 48h;Inert atmosphere; Reflux;
In the reaction flask carbazole 3.0g, meta-bromoiodobenzene 10.15g, 2.39 g copper iodide, 4.95g of potassium carbonate and 40mL of dry xylene, the reaction was refluxed for 48 hours nitrogen, was added 50mL of water quench off the reaction, extracted with dichloromethane, the solvent was evaporated, purified by column chromatography to give a white colored final precipitate 9-(3-bromophenyl)-9H- carbazole 3.5g, 78% yield.
77%
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 3h;Inert atmosphere; Reflux;
S1 (2.25 mmol), S14 (2.35 mmol), (dibenzylideneacetone) dipalladium (0) (0.12 mmol),Sodium tert-butoxide (3.6 mmol) and tri-tert-butylphosphine tetrafluoroborate (0.25 mmol) were placed in a 100 mL three-necked flaskWhile stirring, degassing and nitrogen replacement were repeated 3 times quickly, and 35 mL of toluene was added through a syringe.The mixture was heated under reflux under a stream of nitrogen for 3 hours.After the reaction, water was added to the reaction solution cooled to room temperature, extraction was performed with dichloromethane, and the solution was washed with saturated brine.After the organic layer was dried with anhydrous sodium sulfate, the solvent was distilled off and purified by column chromatography.Intermediate S15 (1.73 mmol, 77%) was obtained.
70%
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 12h;Inert atmosphere;
Under a nitrogen atmosphere (N2 purging), Compound 1G(10 g, 35.48 mmol), 0.6 equivalent of Compound 1H, 0.1 equivalent of CuI, 3.5 equivalents of diaminocyclohexane, and 4.0 equivalents of potassium phosphate were added to 1,4-dioxane(350 ml), and stirred in a 90 C. oil bath. After 12 hours, water was added to the reaction mixture, and extraction was performed. Then, purification was performed using a column using a developing solvent of MC:hexane (5:1) to obtain a white solid 11(7.97 g, yield 70%).
70%
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 80℃;
Sub-1-II-8 (7.94 g, 18.5 mmol) was added to a round bottom flask, N-phenyl-[1,1'-biphenyl]-4-amine (6.82 g, 27.8 mmol) Pd2(dba)3 (0.51 g, 0.6 mmol), P(t-Bu)3 (0.23 g, 1.1 mmol) Add NaO (t-Bu) (5.34 g, 55.6 mol) and toluene (200 mL) and heat at 80 C. After the reaction was completed, distilled water was added, dried over MgSO4 and concentrated. The resulting compound was purified by silicagel column and recrystallized to obtain the product (9.34 g, 85%).
69%
With potassium phosphate; copper(II) iodide; rac-diaminocyclohexane; In 1,4-dioxane; for 16h;Inert atmosphere; Reflux;
In 250mL three-necked flask, were added carbazole 16.72g, m-bromoiodobenzene 42.44g, cuprous iodide 1.9g, 1,2- diaminocyclohexane 3.42g, 42.4g anhydrous potassium phosphate and solvent 1 , 4-dioxane 160mL, N2 replaced three times, heated to reflux and the reaction stopped after 16h.Cooled to room temperature, filtered, and the filtrate was collected, purified by column chromatography (dichloromethane: n-hexane = 1: 1-1: 0), the target receives the solid product 22g (69%).
65%
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 150℃; for 48h;Inert atmosphere;
In a 500 ml single-necked flask, oxazole (10 g, 59.88 mmol), o-bromoiodobenzene (20 g, 71 mmol), copper powder (11.5 g, 180 mmol),K2CO3 (25 g, 180 mmol) was dissolved in 300 ml of dry DMF solvent. Under the protection of N2, the temperature was raised to 150 C and the reaction was carried out for 48 h.After the reaction was terminated, it was cooled to room temperature, extracted, dried, and passed through a column to give a pale yellow liquid, yield 65%.
64.8%
With 18-crown-6 ether; copper; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Sealed tube; Inert atmosphere; Reflux;
1-Bromo-3-iodobenzene (1 g, 3.54mmol),carbazole(0.93 g, 2.94mmol), copper (0.1 g, 0.36mmol), potassium carbonate (1.46 g, 10.6mmol), 18-crown- 6 (0.1 g, 0.36mmol) was placed in a 250 mL three-necked flask, sealed, and 200 mL of N,N-dimethylformamidewas injected under nitrogen atmosphere, and heated to reflux for 24 h. The organic phase was washed three times with water and saturated brine, dried over anhydrous sodium sulfate, and evaporated to remove solvent, using a mixture solvent of PE/EA=8:1 as eluent and silica gel as a stationary phase.Separation and purification by column chromatography.Obtained as a pale yellow solid (0.90 g, yield 64.8%).1H NMR (400 MHz, CDCl3): delta = 8.09 (d,J= 7.6 Hz, 2 H), 7.70 (s, 1 H), 7.54 (d,J= 8.0 Hz, 1 H), 7.46 (d,J= 7.6 Hz, 1 H), 7.41-7.37 (m, 5 H), 7.28-7.25 (m, 2 H).
46%
With potassium carbonate; rac-diaminocyclohexane; copper(l) chloride; In dimethyl sulfoxide; at 110℃; for 16h;Inert atmosphere;
Carbazole (20.0 g, 119.6 mmol), 1-bromo-3-iodobenzene (38.0 g, 134.3 mmol), cuprous chloride (I) (2.37 g, 23.9 mmol), dimethyl sulfoxide (250 ml), potassium carbonate (33.1 g, 239.2 mmol) and 1,2-diaminocyclohexane (6.8 g, 59.8 mmol) were sequentially added to a 500 ml double neck round bottom reaction flask with nitrogen The reaction system was filled, the system was heated to 110 C in an oil bath, and after 16 hours of reaction, the system was cooled and the reaction was poured into 300 ml of water and stirred, followed by extraction with ethyl acetate, and the extract was washed with saturated brine. Then, the water was removed by magnesium sulfate and filtered, and the obtained filtrate was removed by a rotary evaporator, and then silica gel column chromatography and hexane was used as an eluent to obtain a light brown solid which was compound 2-3-b (17.61 g , 46%).
35%
With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 100℃; for 16h;Inert atmosphere; Reflux;
Sigma aldrich in nitrogen (http://www. Sigmaaldrich. Com /) carbazole yarn (50 g, 299. 0 mmol) of toluene 0. 5 L senses a rotation velocity of the disk to, herein 1-bromo-3-iodobenzene sigma aldrich yarn (101. 5 g, 358. 8 mmol), bis (dibenzylideneacetone) palladium (0) (5. 16 g, 8. 97 mmol), tris-tert butylphosphine (3. 02 g, 15. 0 mmol) and sodium tert-butoxide (34. 5 g, 358. 8 mmol) in 100 C sequentially and at the reflux by heating at a 16. Complete after reaction solution at a water doesn't have any error frames, then dichloromethane (DCM) extraction of water to the MgSO4 anhydride after triggers number, filter and was, concentrating it under reduced pressure. Thus-obtained residue number intermediate that is forward separated into flash column chromatography I-2 (33. 3 g, 35%) a obtained
With sodium t-butanolate;1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); In xylene; for 24h;Inert atmosphere; Reflux;
Example 12; Synthesis of Compound 80 Step 1. Carbazole (7.3 g, 43.7 mmol), 3-bromoiodobenzene (25 g, 87.3 mmol) and sodium t-buthoxide (8.4 g, 87.3 mmol) is suspended in 150 mL of dry xylene under nitrogen atmosphere. Tris(dibenzylideneacetone)dipalladium (200 mg) and 1,1'-bis(diphenylphosphino) ferrocene (400 mg) are added as one portion and the reaction is heated to reflux and stirred under nitrogen atmosphere for 24 h. After cooling the xylene is evaporated and the residue is subjected to column chromatography on silica gel, providing 3-bromophenyl carbazole (9.5 g, yellow solidified oil).
With potassium carbonate; In 1,2-dichloro-benzene;
Preparation Example 1 Synthesis of Intermediate 4 g of carbazole, 8.08 g of 1-bromo-3-iodobenzene, 13.2 g of potassium carbonate, 3.08 g of copper powder and 0.63 g of dibenzo-18-crown-6 were dissolved in 30 mL of o-dichlorobenzene, and the resulting solution was refluxed at a steady 100 C. After completion of the reaction, the reaction mixture was extracted with dichloromethane and distilled water, and the solvent was dried. The resulting solid was filtered and purified, yielding 9-(3-bromophenyl)-9H-carbazole as an intermediate.
1.9 g
250ml 3-neck round bottom flask was charged 1-3 (5g), palladium(0)diacetate (0.1g), tri-tert-butylphosphine (0.3g), put the toluene (100ml), 1 h on the atmosphere of argon at room temperature It was stirred. After the addition of potassium carbonate (7.2g), 3- bromo carbazole (6.3g) in the mixture was stirred at 80 C for 6 hours. After the addition of water and extracted with ethyl acetate to give 1.9g the title 1-4 substituents through a separation column using hexane and the resulting material after removal of water.
With dibenzo-18-crown-6; copper; potassium carbonate; In 1,2-dichloro-benzene; at 100℃;
4 g of carbazole, 8.08 g of 1-bromo-3-iodobenzene, 13.2 g of potassium carbonate, 3.08 g of copper powder and 0.63g of dibenzo-18-crown-6 were dissolved in 30 mL of o-dichlorobenzene, and the resulting solution was refluxed at asteady 100C. After completion of the reaction, the reaction mixture was extracted with dichloromethane and distilledwater, and the solvent was dried. The resulting solid was filtered and purified, yielding 9-(3-bromophenyl)-9Hcarbazoleas an intermediate.
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 12h;
At nitrogen environment (N2 purging), 2A, 0.6 equivalent of 2B, 0.1 equivalent of CuI, 3.5 equivalents of diaminocyclohexane, 4.0 equivalents of potassium phosphate were added to 1,4-dioxane And the mixture was stirred in an oil bath at 90 C. Water was added to the reaction mixture after 12 hours, and 2C was obtained as a white solid after extraction using Hexane: MC (5: 1) developing solvent.
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 12h;
In a nitrogen environment and (N2 purging) 5A, 0.6 equivalent of 5B, 0.1 equivalent of CuI,3.5 equivalents of diaminocyclohexane, 4.0 equivalents of potassium phosphate were added to 1,4-dioxaneAnd stirred in an oil bath at 90 C.Water was added to the reaction mixture after 12 hours, and after extraction, white solid 5C was obtained after column using Hexane: MC (5: 1) developing solvent.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 3h;
Synthesis of 3'-Bromo-6-fluoro-2-methoxy-biphenyl To a mixture of 2-fluoro-5-methoxyphenyl boronic acid (1 g, 5.9 mmol, 1 eq.), Pd(PPh3)4 (340 mg, 0.3 mmol, 0.05 eq.) was added toluene (48 ml) and EtOH (12 ml) followed by the 1-bromo-3-iodo benzene (2 g, 7.1 mmol, 1.2 eq) and 2N Na2CO3 aq. (6 ml, 2 eq.). The mixture was stirred at 90 C for 3 hr. After cooling to room temperature, the aqueous layer was separated and the organic layer was dried over MgSO4. Removal of solvent under reduced pressure gave a residue, which was purified by chromatography on silica gel using hexane followed by hexane/EtOAc (20:1) as eluent to give 1.37 g of desired product Int-11 as colorless oil in 83% yield.
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃;Inert atmosphere;
1-bromo-3-iodobenzene (1.118 g, 3.95 mol) and 3-pyridine boronic acid (0.559 g, 4.54 mol) were added to a 100 mL three neck round bottom flask. To this flask, dioxane (20 mL) and aqueous K2CO3 (2 N, 20 mL) were added. The mixture was stirred and degassed with a steam of argon for 30 minutes. Then under argon atmosphere, 50 mg (0.04 mmol) of Pd(PPh3)4 (1%) was added. The mixture was heated to 100 C. and stirred overnight. The next day, the solvent was removed by roto-evaporation and the residue was suspended into an equal amount of water (50 mL) and CH2Cl2 (50 mL). The organic layer was separated from aqueous layer and washed with brine (50 mL×3). After drying over Na2SO4, and removal of the drying agent, about 0.92 g of 3-(3-bromophenyl)pyridine product (100%) was afforded. 1H NMR (400 MHz, CDCl3) 8.85 (s, 1H), 8.65 (d, 1H), 7.87 (d, 1H), 7.75 (s, 1H), 7.57-7.52 (m, 2H), 7.41-7.35 (m, 2H).
90.9%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 18h;Reflux;
<1-g> was synthesized by the following Scheme 7. In a 5000 mL round bottom flask 200.0 g (1.625 mol) of 3-pyridineboronic acid, 549.73 g (1.950 mol) of 1-bromo-3-iodobenzene, 37.60 g (0.033 mol) of tetrakistriphenylphosphinepalladium (Pd (PPh3) 4), 561.60 g (4.063 mol) of potassium carbonate (K 2 CO 3), 500 mL of water, 500 mL of ethanol, and 2000 mL of toluene were added and refluxed for 18 hours.After the reaction is completed, the temperature inside the reactor is cooled to room temperature, the layers are separated using ethyl acetate and water, and the organic layer is concentrated under reduced pressure. After concentration under reduced pressure, using column chromatography 344.4 g (yield 90.9%) of <1-g> were obtained.
88%
With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,2-dimethoxyethane; water; for 18h;Inert atmosphere; Reflux;
A mixture of 3-bromoiodobenzene (19.8 g, 70.0 mmol, pyridine-3- borononic acid (8.6 g, 70.0 mmol) in 1 ,2-dimethoxyethane (315 mL) and 2.0 M aqueous sodium carbonate (105 mL) was sparged with nitrogen for 30 minutes, then palladium acetate (393 mg, 1 .75 mmol) and triphenylphosphine (918 mg, 3.50 mmol) were added and the mixture was heated at reflux for 18 h. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3 x 150 ml_). The combined organic layer was washed with water and brine (2 x 150 ml_ each), then dried over magnesium sulfate, filtered and concentrated to a dark brown oil. The crude product was purified by silica gel MPLC (0 - 90% ethyl acetate in hexanes as eluent). The product fractions eluting when the gradient had reached 55 - 85% ethyl acetate in hexanes were combined and concentrated by rotary evaporation to give 3-(3-bromophenyl)pyridine as a dark yellow oil (14.5 g, 88% yield) having a purity of 97% based on UPLC analysis. This material was taken directly to Step 2.
77%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 95℃; for 24h;Inert atmosphere;
Example 14; Synthesis of Compound 31; A 100 mL, round-bottomed Schlenk flask equipped with a magnetic stir bar was charged with 1-bromo-3-iodobenzene (5.754 g, 20.3 mmol), 3-pyridyl boronic acid (2.5 g, 20.3 mmol), 25 mL of a 2 M aqueous solution of Na2CO3, and 25 mL of 1,4-dioxane. Tetrakis (triphenylphosphine) palladium (0.54 g, 0.5 mmol) was added, the mixture was degassed using five vacuum/nitrogen back-fill cycles, and then was heated to 95 C. for 24 hours with vigorous stirring. The reaction mixture was allowed to cool to room temperature and diluted with CH2Cl2. The organic layer was washed with 1N HCl, H2O, and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The resulting yellow solid was purified by column chromatography on silica gel. Eluent ethyl acetate/hexane (3/97) gave compound 31 as a pale yellow oil 3.6 g (77%). 1H NMR (400 MHz, CDCl3) delta 8.82 (br s, 1H), 8.63 (m, 1H), 7.85 (m, 1H), 7.73 (m, 1H), 7.53 (m, 2H), 7.36 (m, 2H).
46%
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 24h;
149] 3-(3-Bromophenyl)pyridine (lib): A solution of pyridine 3-boronic acid 51 (1.0 g, 8.14 mmol), 3-bromo-l-iodobenzene 50 (2.0 g, 7.07 mmol) and sodium bicarbonate (1.5 g, 17.7 mmol) in dioxane (16 niL) and water (4 mL) was purged with N2 for 5 min.Tetrakis(triphenylphosphine)palladium (400 mg, 0.35 mmol) was added and the mixture was heated at 90 0C for 24 hr. The solution was cooled and the volatile organics were evaporated. The residue was partitioned between EtOAc (50 mL) and water and the layers were separated. The organic layer was washed with water, dried (Na2SO4), and concentrated to give 2.2 g of yellow oil. The crude material was purified on an Analogix automated system (24 g column, 0- 30% EtOAc/heptane) to provide 760 mg (46%) of pure lib. Some impure material was set aside.
With palladium diacetate; sodium carbonate; triphenylphosphine; In water; toluene; for 7.0h;Inert atmosphere; Reflux;
4,4,5,5-tetra-methyl-2-(triphenylene-2-yl) 1,3,2-dioxaborolan 7.08g (20.0mmol), m- bromoiodobenzene16.97g (60.0mmol) , palladium acetate 135 mg (0.60 mmol), triphenylphosphine629 mg (2.40 mmol), sodium carbonate 4.24 g (40.0 mmol), was mixed1,2-dimethoxyethane 100 mL, water 50 mL, under nitrogen atmosphere, 7 It washeated to reflux time. After the reaction, the organic layer was extracted byadding water and ethyl acetate. The organic layer was concentrated underreduced pressure, silica gel column chromatography (developing solvent:toluene) to remove origin ingredients. The solvent was evaporated under reducedpressure, and the resulting solid was dissolved in a small amount of methylenechloride, solid was precipitated with the addition of methanol. The solid wasfiltered, methanol, to give 7.33g of the synthetic intermediate 2 bysequentially washed with hexane (96% yield).
95%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 8.0h;Reflux; Inert atmosphere;
(B-2) Synthesis of intermediate B Under an argon atmosphere, 3.54 g of triphenylene-2-boronic acid piconal ester, 2.83 g of 3-bromoiodebenzene, 0.231 g of tetrakis(triphenylphosphine)palladium (0), 40 mL of toluene and 20 mL of a 2M sodium carbonate aqueous solution were placed in a flask, and refluxed with stirring for 8 hours. After cooling to room temperature, the reaction solution was extracted with toluene. An aqueous phase was removed, and an organic phase was washed with water and saturated brine sequentially, and then dried with magnesium sulfate. Magnesium sulfate was filtered out, and then the organic phase was concentrated. The resulting residue was purified by means of a silica gel column chromatography to obtain 3.64 g (95%) of an intermediate B.
2-bromopyridine 6.0g (38.0 mmol) was dissolved in tetrahydrofuran, 300ml, was added to Tetrakistriphenylphosphine Pd (0) 2.2g (1.9 mmol) was stirred at room temperature for about 5 minutes. Thereafter, by the addition of 1-Bromo-3-iodobenzene 10.8g (38.0 mmol) of potassium carbonate and 10.5g (76.0 mmol). Then, when the mixture was heated under reflux for one day at 70 was added distilled water 150ml It turned on. When the reaction is complete, the extract was added to 100ml of ethyl acetate, and distilled under reduced pressure the organic layer was dried over magnesium sulfate. Purification by the results obtained from this by column chromatography to yield the intermediate 1-2 about 7.6g (32.3 mmol, 85percent yield). The resulting compound was confirmed by LC-MS.
Reference Example 28; Preparation method of 2-(3-bromophenyl)pyridine; In the same manner as in Reference Example 25, except that a solution of tert-butyllithium in n-pentane was used instead of n-butyllithium, and 0.63 ml of 2-bromopyridine was used instead of 4-bromopyridine, 845 mg of the title compound was obtained. Physicochemical properties of this compound (1) Molecular formula: C11H8BrN (2) Mass spectrum (EI): m/z 233 (M)+ (3) 1H NMR spectrum (300 MHz, CDCl3) delta (ppm): 7.25 (ddd, pyridine), 7.33 (m, C6H4), 7.53 (ddd, C6H4), 7.69 (ddd, pyridine), 7.75 (ddd, pyridine), 7.90 (ddd, C6H4), 8.17 (dd, C6H4), 8.69 (ddd, pyridine).
With copper; potassium carbonate; In dichloromethane; water;
Synthesis Example 3 Synthesis of N-(3-bromophenyl)carbazole (compound 4) Under nitrogen, carbazole (24.3 g, 1 eq.) is added to a flask together with 1-bromo-3-iodobenzene (98%; 75.3 g, 1.9 eq.), potassium carbonate (48.2 g, 2.5 eq.) and copper (1.77 g, 0.1 eq.). The reaction is heated to 150 C. and stirred at 150 C. for 48 h. The mixture is cooled to room temperature and diluted with 150 mL of methylene chloride. 100 mL of demineralized water are added to the mixture, which is stirred. Removal of the aqueous phase is followed by washing a further 2* with demineralized water (100 mL). The organic phase is dried over sodium sulfate and concentrated. The excess 1-bromo-3-iodobenzene is distilled off under reduced pressure. LC (SiO2; cyclohexane/methylene chloride 95:5) gives 37.1 g of product (82.4% yield). 1H NMR (CD2Cl2, 400 MHz): delta=8.13 (d, 2H), 7.75 (s, 1H), 7.61 (d, 1H), 7.53 (d, 1H), 7.49 (d, 1H), 7.42 (m, 4H), 7.27-7.31 (m, 2H)
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In ethanol; water; toluene; at 70℃; for 4h;
To a solution of pyrimidine-5-boronic acid (4.0 g, 32.2 mmol) in H20:EtOH:Toluene (80.0 mL, 16:32:32 mL) was added l-bromo-3iodobenzene (4.1 mL, 32.2 mmol), potassium carbonate (8.9 g, 64.4 mmol) and Pd(dppf)Cl2 (2.4 g, 3.2 mmol). The reaction mixture was stirred at 70C for 4 hour. The reaction was partitioned with EtOAc (400 mL) and H20 (200 mL). The organic phase was separated and washed with brine twice, then filtered over a pad of celite. Filtrate was partitioned in seperatory funnel and organic phase was washed with brine, dried over Na2S04, filtered and concentrated. The resulting crude product was purified by Teledyne-Isco flash system by using EtOAc/Hexane, 0 to 30% of ethyl acetate in hexane to provide compound II as light pink solid (6.4 g, 82% yield). XH NMR (400 MHz, DMSO- d6) delta (ppm): 9.21 (s, 1H), 9.17 (s, 1H), 8.06 (s, 1H), 7.83 (d, 1H), 7.68 (s, 1H), 7.50 (t, 1H).
70%
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 24h;Reflux; Inert atmosphere;
2.0 g of compound 19 (16.1 mmol), 4.6 g of compound 16 (16.1 mmol), 930 mg of Pd(PPh3)4 (0.81 mmol), 4.3 mL of K2CO3 (2M in H2O), 100 mL of toluene and 50 mL ethanol were added to a 500 mL two-necked flask and heated to reflux for 24 hours under nitrogen gas. After returning to room temperature, the resulting solution was extracted using 20 mL of dichloromethane for several times. The organic layer was then washed with saturated saline and collected. After removal of water of the collected solution by adding dry magnesium sulfate, filtered and concentrated by reducing the pressure, the concentrated results were purified using column chromatography (silicon dioxide, trichloromethane/ethyl acetate=3/1). Thus, 7.5 g of colorless liquid product (compound 20) was obtained, with a yield of 70%.
63%
With sodium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; for 18.5h;Reflux; Inert atmosphere;
Example 1This example illustrates the synthesis of Compound 1 , 5-[3- (4,6-bis-(3-biphenyl)-2-pyrimidinyl)phenyl]pyrimidine.(1 a) 5-(3-Bromophenyl)pyrimidineA 1000 mL 3-neck round-bottomed flask equipped with a condenser, thermometer and side arm stopper was charged with a suspension 3-bromoiodobenzene (19.80 g, 70.0 mmol), pyrimidine-5- borononic acid (8.67 g, 70.0 mmol) in 1 ,2-dimethoxyethane (315 mL) and sodium carbonate (22.26 g, 210.0 mmol) in deionized water (105 mL). The mixture was sparged with nitrogen for 30 minutes, then palladium acetate (393 mg, 1 .75 mmol) and triphenylphosphine (918 mg, 3.50 mmol) were then added. The reaction mixture was heated at reflux for 18 h then cooled to room temperature after it was determined by UPLC to be complete. The biphasic reaction mixture was extracted with EtOAc (3 x 150 mL). The combined organic layer was washed with water and brine (2 x 150 mL, each), then dried over MgSO4, filtered and concentrated to an off-white solid that was purified by MPLC (hexanes/CHCI3 followed by crystallization from absolute ethanol (approximately 200 mL) to give the desired product, 5-(3-bromophenyl)pyrimidine (8.62 g, 63% yield). UPLC analysis of this material showed it to have a purity of 97.8%.
2.42 g
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In ethanol; water; toluene; at 20 - 150℃; for 2.017h;
Pyrimidine-5-boronic acid (13) (2.0 g, 16.1 mmol) was dissolved in mixture of water (8 mL), ethanol (16 mL) and toluene (16 mL) and 1-bromo-3-iodobenzene (4.57 g, 16.1 mmol) followed by potassium carbonate (4.46 g, 32.3 mmol, 2 eq) and Pd(dppf)Cl2 (1.18 g, 1.61 mmol, 0.1 eq) were added. Mixture was stirred at room temp for 1 min and temperature was increased slowly to 150 C over 2 hrs. Mixture was allowed to cool to room temperature, and poured into mixture of 200 mL of ethyl acetate and 100 mL of water, shaken well, organic layer separated and washed with brine 2x, filtered through pad of Celite, dried with anh. sodium sulfate, filtered and concentrated. Product 5-(3- bromophenyl)pyrimidine (14) was purified by flash chromatography, yield 2.42 g, light- pink solid.
With potassium carbonate; In hexane; dichloromethane;
Example 9 Synthesis of Carbazole Derivative 9 3,6-Diphenylcarbazole (2.80 g, 8.77 mmol), 1-bromo-3-iodobenzene (22.18 g, 87.7 mmol), copper powder (0.279 g) and potassium carbonate (4.85 g) were mixed together, and the mixture was heated in a nitrogen atmosphere at 190° C. for 9 hours. The resultant mixture was cooled to room temperature and diluted with methylene chloride, followed by washing with water and drying, to thereby obtain a pale brown liquid. Next, the obtained liquid is purified through silica gel column chromatography using a solvent mixture of methylene chloride/hexane (2/3 by volume), to thereby obtain 3.59 g of 9-(3-bromophenyl)-<strong>[56525-79-2]3,6-diphenylcarbazole</strong>.
3.59 g
With copper; potassium carbonate; at 190℃; for 9h;Inert atmosphere;
3,6-Diphenylcarbazole (2.80 g, 8.77 mmol), 1-bromo-3-iodobenzene (22.18 g, 87.7 mmol), copper powder (0.279 g) and potassium carbonate (4.85 g) were mixed together, and the mixture was heated in a nitrogen atmosphere at 190° C. for 9 hours. The resultant mixture was cooled to room temperature and diluted with methylene chloride, followed by washing with water and drying, to thereby obtain a pale brown liquid. Next, the obtained liquid is purified through silica gel column chromatography using a solvent mixture of methylene chloride/hexane (2/3 by volume), to thereby obtain 3.59 g of 9-(3-bromophenyl)-<strong>[56525-79-2]3,6-diphenylcarbazole</strong>.
With ammonium hydroxide; 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane; palladium diacetate; In toluene; at 120℃; under 5171.62 Torr; for 20h;Autoclave;
General procedure: To a 45 mL glass-lined autoclave, 1 (0.5 mmol), Pd(OAc)2 (0.01mmol), CYTOP292 (0.02mmol), aqueous ammonia (0.2 mL) and toluene (10 mL) were sequentially added. After sealing, the autoclave was purged three times with carbon monoxide and pressurized with 100 psi of CO. The resulting mixture was then heated at 100 C for 20 h. The autoclave was removed from the oil bath and cooled to room temperature prior to the release of excess carbon monoxide. The reaction mixture was concentrated by rotary evaporator, and purified by flash chromatography on silica gel with a mixture of hexanes and ethyl acetate (2:1to 1:2) as the eluent to afford the products.
With 2-Picolinic acid; copper(l) iodide; caesium carbonate; In 1,4-dioxane; at 70℃;Inert atmosphere;
General procedure: General procedure for the synthesis of alpha-arylacetic acid tert-butyl esters: A Schlenk tube was charged with aryl iodide (1.0mmol), CuI (9.5mg, 0.05mmol), 2-picolinic acid (12mg, 0.10mmol), and cesium carbonate (978mg, 3.0mmol). The tube was evacuated and backfilled with argon three times before tert-butyl acetoacetate (2.0mmol) and 2mL of 1,4-dioxane was added. The tube was immersed in an oil bath, and the reaction mixture was stirred at the indicated temperatures for 33-48h. The cooled mixture was partitioned between ethyl acetate and saturated NH4Cl, the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with PE/EA=20:1 to 3:1) to provide the desired alpha-arylacetic acid tert-butyl esters.
With triethylamine; In N,N-dimethyl-formamide; at 100℃; for 2h;Inert atmosphere;
General procedure: A mixture of 10 mg supported catalyst, 0.2 mmol (22 l)iodobenzene, 0.4 mmol (36 l) methyl acrylate, 0.68 mmol (100 l)Et3N and 1 ml DMF was stirred in an inert atmosphere at 100C for2 h. The solution was removed by a syringe and the catalyst was reused without purification. Reaction mixtures were analysed by gas chromatography(Hewlett Packard 5890) and GC-MS (Hewlett Packard 5971AGC-MSD, HP-1 column). Conversions and selectivities of the reactions were determined by GC.
With triethylamine; In N,N-dimethyl-formamide; at 100℃; under 750.075 Torr; for 8h;Schlenk technique; Inert atmosphere;
General procedure: In a typical experiment a solution containing the palladiumcatalyst (with 6 mol Pd-content) was placed in a Schlenk-tube.Under argon, 0.2 mmol (22.5 l) iodobenzene (1), 0.5 mmol aminereagent, 0.7 mmol (100 l) triethylamine and 1 ml solvent wasadded and the atmosphere was changed to carbon monoxide. Thereaction mixture was heated with stirring in an oil bath at 100Cand was analysed by gas chromatography.
With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12h;Inert atmosphere;
General procedure: General procedure for the palladium-catalyzed reaction A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51 mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2 (3*3 mL). The chemoselectivity (3aa/4aa=92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2=97/3) as a white solid.
With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12.0h;Inert atmosphere;
General procedure: General procedure for the palladium-catalyzed reaction A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51 mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2 (3*3 mL). The chemoselectivity (3aa/4aa=92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2=97/3) as a white solid.
With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12h;Inert atmosphere;
General procedure: General procedure for the palladium-catalyzed reaction A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51 mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2 (3*3 mL). The chemoselectivity (3aa/4aa=92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2=97/3) as a white solid.
10-(3-bromophenyl)-9,9-diphenyl-9,10-dihydroacridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; for 8h;Inert atmosphere; Reflux;
Under an argon (Ar) atmosphere, 200 mL of toluene and 1.0 g of Xantphos were added in order to a mixture of 6.0 g of Compound D, 5.1 g of Compound B, 0.39 g of palladium acetate and 5.2 g of sodium-tert-butoxide, and the resulting mixture was heated to reflux for about 8 hours. After cooling to ambient temperature, the reaction solution was filtered and 100 mL of ethanol was added to the filtrate. Precipitated crystals were filtered and washed in order with 50 mL of water and 100 mL of ethanol. The crystals were dissolved in toluene and purified by silica gel column chromatography (toluene:hexane 1:1) to obtain 7.2 g (yield 81%) of Compound G as a light yellow powder.
58%
With copper(l) iodide; sodium t-butanolate; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 100℃; for 12h;
24 g (72 mmol) of Intermediate I-3-2, 24 g (86 mmol) of 1-bromo-3-iodobenzene, 0.685 g (3.6 mmol) of copper iodide, 13.83 g (143.96 mmol) of sodium tert-butoxide, 1,644 g (14.40 mmol) of trans-1,2-diaminocyclohexane, and 150 ml of 1,4-dioxane were allowed to react at a temperature of 100 C. for 12 hours. After the reaction mixture was cooled to room temperature, methanol was added thereto to produce precipitates that were subsequently separated by a filter. The separated precipitates were purified using column chromatography, thereby obtaining 20.2 g (yield: 58%) of Intermediate I-3-3.
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 70℃; for 5h;
To a solution of 1-bromo-3-iodobenzene (4.0 g, 14.1 mmol) in DMSO (40 mL) were added 3-aminopropanenitrile (1.5 mL, 20 mmol) , cuprous iodide (2.8 g, 15 mmol) , cesium carbonate (7.0 g, 21.5 mmol) and N, N-dimethylglycine (1.5 g, 14 mmol) in turn. The mixture was stirred at 70 for 5 h and quenched with water (40 mL) . The resulting mixture was extracted with DCM (40 mL × 3) . The combined organic layers were dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted withPE/EtOAc (v/v) 2/1 to give a light yellow oily product (3.0 g, 94) .[0990]MS (ESI, pos. ion) m/z: 225.0, 227.0 [M+1]+
94%
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 70℃; for 5h;Inert atmosphere;
oBromonium iodobenzene(4.0 g, 14.1 mmol) in dimethylsulfoxide (40 mL) was added <strong>[151-18-8]3-aminopropionitrile</strong>(1.5 mL, 20 mmol), cuprous iodide (2.8 g, 15 mmol), cesium carbonate (7.0 g, 21.5 mmol) and N, N-dimethylglycine(1.5 g, 14 mmol), reacted at 70 C for 5 hours, quenched with water (40 mL), extracted with dichloromethane (40 mL x 3), dried over anhydrous sodium sulfate (Eluent: PE / EtOAc (v / v) = 2/1) to give 3.0 g of a pale yellow oil, and the residue was subjected to column chromatography , Yield: 94%.
5-(3-bromophenyl)-5H-pyrido[3,2-b]indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70.3%
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate; In 1,4-dioxane; at 100℃;Inert atmosphere;
One 100 mL Flask in delta-carboline 1.0 g (5.95 mmol), 1-bromo-3-iodobenzene 1.13 mL (8.92 mmol) and CuI 566 mg (2.98 mmol), CS2CO3 3.9 g (11.9 mmol) and 1,10-phenanthroline1 .07 g (5.95 mmol)And the mixture was dissolved in 1,4-dioxane 30 mL under a nitrogen atmosphere At 100 was stirred under reflux. After the reaction was cooled to room temperature and terminated into a 50 mL MC in the solid mixture was filtered and concentrated under reduced pressure of the filtrate. Purification of the resulting compound was purified by silica gel column chromatography to obtain a compound (intermediate (9)), 1.35 g (yield: 70.3%) of a white solid was obtained.
64%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80 - 100℃; for 24h;Inert atmosphere;
2 opening 250 ml multi function cap to delta-carboline (15g, 89mmol), 1-bromo-3-iodobenzene (37.8g, 134mmol), CuI (1.1g, 5.79mmol), 1, 10-phenanthroline (2g, 11.13mmol), K 3 PO 4 (47g, 220mmol), Dioxane (300 ml) together in a under nitrogen into the 80-100 o C in the reflux time 24. After reaction is completed, melt to MC Celite filter section. After distillation the pressure-reducing solution one filter, out by extracting with distilled water and a Methylene Chloride. Extracted Methylene Chloride layer MgSO 4 after for holding a order to form an exterior, of methanol removing the solvent by the yellow solid obtained. The solid white Column Chromatography method using a solid (16) separated the. (18g, 64%)
64%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80 - 100℃; for 24h;Inert atmosphere; Reflux;
delta-carboline in 250ml two-necked flask (15g, 89mmol), 1-bromo-3-iodobenzene (37.8g, 134mmol), CuI (1.1g, 5.79mmol), 1,10-phenanthroline (2g, 11.13mmol), K3PO4 (47g, 220mmol), put as the Dioxane (300ml) was refluxed for 24 hours at 80 ~ 100oC under nitrogen. After the reaction was completed, the Celite filter was dissolved in MC. Filter the solution and then distilled under reduced pressure, and distilled water was extracted with Methylene Chloride. After japahjun moisture Methylene Chloride the extracted layer with MgSO4, the solvent was removed by distillation under reduced pressure to give a yellow solid. This solid was isolated using the Column Chromatography how the white solid (16). (18g, 64%)
64%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80 - 100℃; for 24h;Inert atmosphere;
2-necked 250ml flask was charged with delta-carboline (15g, 89mmol), 1-bromo-3-iodobenzene (37.8g, 134mmol), CuI (1.1g, 5.79mmol), 1,10-phenanthroline (2g, 11.13mmol), K3PO4 (47g, 220mmol), put as the Dioxane (300ml) was refluxed for 24 hours at 80 ~ 100oC under nitrogen. After the reaction was completed, the Celite filter was dissolved in MC. Filter the solution and then distilled under reduced pressure, and distilled water was extracted with Methylene Chloride. After japahjun moisture Methylene Chloride the extracted layer with MgSO4, the solvent was removed by distillation under reduced pressure to give a yellow solid. This solid was isolated using the Column Chromatography the white solid (16). (18g, 64%)
62%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80 - 100℃; for 24h;Inert atmosphere;
In a two-neck 250 ml flask, 15 g (89 mmol) of delta-carboline,1-Bromo-3-iodobenzene(1-bromo-3-iodobenzene) 37.8 g (134 mmol),1.1 g (5.79 mmol) CuI,1, 10-phenanthroline 2g (11.13 mmol),47 g (220 mmol) of K3PO4, 300 ml of dioxaneAnd refluxed in a nitrogen atmosphere at 80 to 100 C for 24 hours.After the reaction is complete,The reaction was dissolved in MC and filtered using Celite.The filtered solution was distilled under reduced pressure, then extracted with methylene chloride and distilled water. The extracted methylene chloride layer was dehydrated with MgSO4 and the solvent was removed by vacuum distillation to obtain a yellow solid.The white solid (3) was isolated (18.0 g, yield: 62%) by Column Chromatography method.
62%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80 - 100℃; for 24h;Inert atmosphere;
In a 250 ml two-necked flask, 15 g (89 mmol) of porphyrin (delta-carboline), 37.8 g (134 mmol) of 1-bromo-3-iodobenzene (1-bromo-3-iodobenzene), 1.1 g ( 5.79 mmol) of CuI, 2 g (11.13 mmol) of 1,10-phenanthroline (1,10-phenanthroline), 47 g (220 mmol) of K3PO4, 300 ml of dioxane (Dioxane) in a nitrogen atmosphere at 80-100 C reflux for 24 hours. After completion of the reaction, the reaction was dissolved in MC and filtered through Celite. The filtered solution was subjected to distillation under reduced pressure, and then extracted with dichloromethane and distilled water. After extracting the extracted dichloromethane layer with M gSO 4 to remove water, the solvent was evaporated under reduced pressure to give a yellow solid. The solidThe white solid (3) (18.0 g, yield: 62%) was isolated by the column chromatography (Column Chromatography).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 24h;Inert atmosphere;
Compound 7 (5.24 g, 87 mmol) was added to a 250 ml single-necked flask. m-bromoiodobenzene (8.43 g, 29.8 mmol), 40 ml of a 2 M aqueous potassium carbonate solution was dissolved in a solvent of 40 ml of ethanol and 80 ml of toluene.Under the protection of N2, Pd(PPh3)4 (0.2 g, 0.15 mmol) was added. The temperature was slowly raised to 100 C, and the mixture was reacted under reflux for 24 hours.After cooling, the layers were separated, the organic layer was evaporated, and then evaporated to give 6.5 g of product. Yield: 80%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12.0h;Inert atmosphere;
Nitrogen environment from intermediate I-8 (50 ug, 116 mmol) dmf tetrahydrofuran (THF) 0.5 L dissolved after, here in 1-bromo-3-iodobenzene (39.4 g, 139 mmol) and tetrakis (triphenylphosphine) palladium (1.34 g , when the stirring 1.16 mmol)It turned on. Into the potassuim carbonate (40.1 g, 290 mmol) in saturated water it was heated to reflux at 80 for 12 hours. After the reaction was completed, the reaction solution into water and extracted with dichloromethane (DCM) and then water was removed with anhydrous MgSO4, filterFrom a reduced pressure and concentrated. Thus, the obtained residue was purified by flash column chromatography purification Intermediate I-9 (42.6 g, 80%) as to obtain a.
80%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12.0h;Inert atmosphere;
Under a nitrogen atmosphere, 50g (116mmol) Compound I-3 was dissolved in 500ml of tetrahydrofuran was added 39.4g (139mmol) 1- bromo-3-iodobenzene and 1.34g (1.16mmol) of tetrakis (triphenylphosphine) thereto palladium, and the mixture was stirred. Subsequently, to which was added 40.1g (290mmol) of potassium carbonate saturated aqueous mixture was heated at reflux for 12 hours and at 80 . When the reaction was completed, water was added to the reaction solution, and the mixture was extracted with methylene chloride, dried with anhydrous MgSO4 followed by removal of water filtered and concentrated under reduced pressure. Subsequently, the obtained residue was separated therefrom and purified by column chromatography to give 42.6g (80%) Compound I-6.
80%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12.0h;Inert atmosphere;
Inthe nitrogen ambient, after the compound I-3 50 g (116 mmol) was melted in thetetrahydrofuran (THF) 0.5 L here 1- bromo -3- iodobenzene(1-bromo-3-iodobenzene) 39.4 g (139 mmol) and tetrakis (triphenylphosphine)palladium (tetrakis(triphenylphosphine)palladium) 1.34 g (1.16 mmol) were putand it mixed. The saturated potassium carbonate 40.1 g (290 mmol) was put inwater and it heated up in 80 for 12hours and it refluxed. After water was put in into the reaction solution afterthe reaction completion and it extracted in the dichloromethane (DCM) moisture wasremoved to the anhydrous MgSO4 it filtered and it was concentrated underreduced pressure. The residue obtained in this way was refined to the flashcolumn chromatography after dividing and the compound I-6 42.6 g (80 %) wasobtained.
80%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12.0h;Inert atmosphere;
Nitrogen environment in the compound I-3 50 g (116 mmol) of tetrahydrofuran (THF) and then dissolved in 0.5 L, here 1-bromo-3 - iodo-benzene (1-bromo-3-iodobenzene) 39.4 g Insert (139 mmol) and tetrakis (triphenylphosphine) palladium (tetrakis (triphenylphosphine) palladium) 1.34 g (1.16 mmol) was stirred.Into a potassium carbonate 40.1 g (290 mmol) in saturated water it was heated to reflux at 80 for 12 hours.After the reaction was completed, the reaction solution into water, extracted with dichloromethane (DCM) and then water was removed with anhydrous MgSO4, filter and was concentrated under reduced pressure.Thus the resulting residue was separated and purified by flash column chromatography to give the compound I-6 42.6 g (80%).
80%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12.0h;Inert atmosphere;
In a nitrogen atmosphere, 50 g (116 mmol) of Intermediate I-3Was dissolved in 500 ml of tetrahydrofuran,39.4 g (139 mmol) of 1-bromo-3-iodobenzene was added thereto,And tetrakis (triphenylphosphine) palladium 1.34 g (1.16 mmol) was added thereto and stirred. 40.1 g of potassium carbonate saturated in water (290 mmol) was added thereto,The mixture was heated 80C reflux for 12 hours.After completion of the reaction, water was added to the reaction solution, and dichloromethane After extraction, water was removed with anhydrous MgSO4, Filtered and concentrated under reduced pressure.The thus-obtained residue was separated by column chromatography Purification yielded 42.6 g (80%) of intermediate I-6.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene;Inert atmosphere; Reflux;
2b:To 2a (19.9g, 83 . 6mmol) and 1-bromo-3-iodobenzene(23.48g, 83 . 0mmol) in 200 ml of a toluene solution of 100 ml of distilled water and 50 ml ethanol. Added sodium carbonate (21.99g, 207 . 5mmol). Carefully argon degassing of the suspension was done. Subsequently added tetrakis(triphenylphosphine) palladium (0) (3.44g, 2 . 98mmol). The reaction mixture was heated to reflux and stir overnight. After the cooling to room temperature, the use of under cooling 6MHCl acid to the reaction mixture is carefully and pH-7. The aqueous phase is extracted using acetic acid ethyl ester. Combined with the phase and saturated NaCl aqueous solution used for washing, drying with sodium sulfate. After removing the solvent in a vacuum, through the use of 1:9 ethyl acetate/toluene as eluent of the column chromatography purification of the solid residue. The crude product is further by heptane/ethyl acetate solvent mixture in order to get the solid is recrystallized 2b (7.8g).
500ml round bottom flask was placed 1-bromo-3-iodo-benzene (25.0g, 88mmol) was dissolved into 200ml of tetrahydrofuran. The reaction solution was cooled road -78 under a nitrogen atmosphere. A n-butyllithium (60.75ml, 97mmol) to the cooled solution was slowly added dropwise thereto for 30 minutes, the mixture was stirred for 1 hour at the same temperature. Trimethyl borate (11g, 106mmol) were added dropwise at the same temperature the mixture was stirred at room temperature overnight. It was acidified by dropwise addition of 2 normal hydrochloric acid to the reaction solution, which was stirred for 1 hour. Extraction with ethyl acetate was separated organic layer was concentrated under reduced pressure, crystallization was put in a cold n-hexane. Intermediate 11-a> was obtained. (12g, 67.6percent).
67.6%
Insert the 1-bromo-3-iodo-benzene (25.0g, 88mmol) in 500ml round bottom flask was put in a 200ml tetrahydrofuranDissolved.The reaction solution was cooled road -78 under a nitrogen atmosphere.It was slowly added dropwise for 30 minutes n-butyllithium (60.75ml, 97mmol) to the cooled solution,It was stirred for 1 hour at the same temperature.Trimethyl borate (11g, 106mmol) were added dropwise at the same temperature the mixture was stirred at room temperature overnight. It was acidified by dropwise addition of 2 normal hydrochloric acid to the reaction solution, which was stirred for 1 hour. Ethyl acetate was extracted with Tay organic layer was separated and concentrated under reduced pressure, crystallized into the cold n-hexane it was obtained (12g, 67.6percent).
With copper; potassium carbonate; sodium sulfate; In nitrobenzene; at 250℃; for 12h;Inert atmosphere;
Nitrogen airflow under <strong>[6960-42-5]7-nitro-1H-indole</strong> (11.2 g, 69.0 mmol), 1-bromo-3-iodobenzene (19.5 g, 69.0 mmol), cu powder (0.45 g, 6.90 mmol), K 2 CO 3 (18.9 g, 138.0 mmol), Na 2 SO 4 (19.5 g, 138.0 mmol), nitrobenzene (250 ml) 12 for mixing and 250 C in adaptation stirring time. Nitrobenzene after completion to remove the methylene chloride organic separating the MgSO 4 was using order to remove the water and to. Evaporating a solvent from an organic layer water is removed after removing the column chromatography for purifying the 1-(3-bromophenyl)-<strong>[6960-42-5]7-nitro-1H-indole</strong> (14.2 g, yield 65%)is obtained.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; at 80℃; for 12h;Inert atmosphere;
Nitrogen environment in the compound I-8 (50 g, 140 mmol) and tetrahydrofuran (THF) 0.45 L dissolved after, here in 1-bromo-3-iodobenzene (43.7 g, 154 mmol) and tetrakis (triphenylphosphine) palladium (1.62 g and stirred into a 1.40 mmol). Into the potassuim carbonate (48.4 g, 350 mmol) in saturated water it was heated to reflux at 80 for 12 hours. After the reaction was completed, the reaction solution into water and extracted with dichloromethane (DCM), and then removing water by anhydrous MgSO4 One was then filter, and concentrate under reduced pressure. The obtained residue was purified by flash column chromatography to give the compound I-15 (41.5 g, 77%).
77%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 10h;Reflux; Inert atmosphere;
196.48 mmol) of Intermediate L-5, 72.26 g (255.42 mmol) of 1-bromo-3-iodebenzene, 54.31 g (392.96 mmol) of potassium carbonate, Pd (PPh3) ) Was added to 400 mL of tetrahydrofuran and 200 mL of water, and the mixture was heated under reflux for 10 hours under a nitrogen stream. The resulting mixture was added to 1500 mL of methanol, and the crystallized solid was filtered, and then dichloromethane was dissolved. The mixture was filtered through silica gel / celite, and an organic solvent was removed in an appropriate amount. The residue was recrystallized from methanol to obtain 3-bromo-5'-phenyl The yield of compound 3-bromo-5'-phenyl-1,1 ': 3,1 "-terphenyl (58.63 g, 77% The results of the analysis are as follows.
With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; for 24h;Reflux;
500 mL of the reactor to 20.7 g (127mmol), 1-bromo-3-iodobenzene 24.8 g (127mmol), copper powder 5.6 g (83mmol), 18 - crown-6-ether, 4.6 g ( 82 mmol), into potassium carbonate 24.2 g (275mmol), dichloro benzene was stirred under reflux for 24 hours. After the reaction dichloromethane to remove the benzene, and separated by column chromatography with methylene chloride and heptane to give a 21 g. (Yield: 81.6%)
With palladium diacetate; potassium carbonate; tris-(o-tolyl)phosphine; In ethanol; water; toluene; at 80℃; for 14h;Inert atmosphere;
3 - (9H-carbazole-9-yl) phenylboronic acid 16g (56mmol), 3-iodo Dove our benzene 19g (67mmol), tri(ortho-tolyl)phosphine 0.68g (2.2mmol), 2M aqueous potassium carbonate solution 56mL, 250mL of toluene, 30mL of ethanol were put into a flask 1L 3 areas, followed by replacing the air in the flask with nitrogen.Put 0.13g of palladium acetate (0.56mmol) in a mixture, the mixture was stirred at 80 heating for 14 hours.Extract the aqueous layer of the reaction mixture with toluene and the combined extract solution was obtained and the organic layer was washed with water and a saturated sodium chloride solution.Drying over magnesium sulfate was added to the organic layer and, by nature of the obtained mixture was filtered to obtain a filtrate.The filtrate was concentrated to give an oil.An oil using the LC-SakuraNEXT was purified by recycle preparative HPLC.The obtained fractions were concentrated, washed with methanol and toluene, 9- [3- (3-bromophenyl) phenyl] -9H- to give the carbazole as a white solid in 58percent yield 13g.For step 1 it was shown in the synthesis scheme (a-2).
2.6 g
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃;Inert atmosphere;
100ml 3-neck round bottom flask was added Intermediate 1-5 (3g), into 1-bromo-3-iodo-benzene (3.8g), tetrahydrofuran (60ml), potassium carbonate (3g) and water (11ml) was stirred It was. Put the tetrakis (triphenylpohsphine) palladium(0) (0.13g) in a mixed liquid was heated to 80 . Separating the reaction solution layer was removed by the water and the organic layer was washed twice with water. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to remove the solvent. Through a column separation process using hexane The material produced by the concentrated to give 2.6g of the title 3-1 substituents.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;
In the nitrogen ambient, after 2 -(biphenyl-3-yl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolanes (20 g, 71 mmol) weremelted in the THF (Tetrahydrofuran) 1 L here 1-bromo-3-iodobenzenes (22 g, 78mmol) and tetrakis (triphenylphosphine) palladium(Pd(PPh(sub)3(/sub))(sub)4(/sub)) (0.8 g, 0.71 mmol) were put and it mixed.Saturated potassuim carbonate (K(sub)2(/sub)CO(sub)3(/sub)) (25 g, 177 mmol)were put in water and it heated up in 80for 12 hours and it refluxed. After water was put in into the reaction solutionafter the reaction completion and it extracted in the dichloromethane (DCM)moisture was removed to the anhydrous MgSO4 it filtered and it was concentratedunder reduced pressure. The residue obtained in this way was refined to theflash column chromatography after dividing and intermediate I-1s (20 g, 91 %)were obtained.
91%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;
Synthesis Example 9: Synthesis of Intermediate I-9 Compound I-8 (20 g, 71 mmol) was dissolved in THF (1 L) under a nitrogen environment, 1-bromo-3-iodobenzene (22 g, 78 mmol, TCI) and tetrakis(triphenylphosphine)palladium (0.8 g, 0.71 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (25 g, 177 mmol) was added thereto, and the mixture was heated and refluxed at 80 C. for 12 hours. When the reaction was complete, water was added to the reaction solution, and the mixture was extracted with dichloromethane (DCM) and then, filtered after removing moisture with anhydrous MgSO4 and concentrated under a reduced pressure. This obtained residue was separated and purified through flash column chromatography to obtain Compound I-9 (20 g and 91%). HRMS (70 eV, EI+): m/z calcd for C18H13Br: 308.0201. found: 308. Elemental Analysis: C, 70%; H, 4%
With copper; potassium carbonate; In nitrobenzene; at 190℃; for 12h;Inert atmosphere;
Preparing said under airflow nitrogen obtained at the 3 e.g. IC-3 (18.85 g, 46.17 mmol), 1-bromo-3-iodobenzene (19.59 g, 69.26 mmol), cu powder (0.29 g, 4.62 mmol), K2CO3(6.38 g, 46.17 mmol), nitrobenzene (200 ml) for mixing and 190? In adaptation stirring time 12.Nitrobenzene after completion to remove the methylene chloride organic separating the MgSO4was using order to remove the water and to. Evaporating a solvent from an organic layer water is removed after removing the column chromatography (Hexane: MC = 3:1 (v/v)) for purifying the IC-4 (20.81 g, 80% yield) a obtained.
54%
With copper(l) iodide; potassium carbonate; ethylenediamine; In toluene; at 120℃; for 47h;Inert atmosphere;
First, 6.0 g (15 mmol) of 9-phenyl-3,3?-bi-9H-carbazole, 8.3 g (29 mmol) of 3-bromoiodobenzene, 6.2 g (29 mmol) of potassium carbonate, 1.5 g (24 mmol) of ethylenediamine (abbreviation: EDA), and 2.5 g (13 mmol) of copper iodide were put in a three-neck flask equipped with a reflux pipe, and the air in the flask was replaced withnitrogen. To this mixture was added 100 mL of toluene, and the mixture was heated at120 C for 47 hours under a nitrogen stream. Water was added to the obtained reaction liquid, and the reaction liquid was subjected to extraction with ethyl acetate. The obtained solution of the extract was washed with saturated brine. Magnesium sulfate was added and filtration was performed. The solvent of the obtained filtrate wasdistilled off Purification was conducted by silica gel column chromatography using a1:3 toluene-hexane mixed solvent as the developing solvent to give 4.5 g of the desiredsubstance (as a yellow solid in a yield of 54 %). The synthesis scheme of Step 1 isshown in the following equation (A-3).
52%
With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; at 120℃; for 12h;
9-phenyl-9H, 9?H-3,3?-bicarbazole (20g, 0.049mol),1-bromo-3-iodobenzene (28 g, 0.098 mmol), CuI (9.32 g, 0.049 mol),K3PO4 (26g, 0.12mol), ethylenediamine (3.3mL) and toluene (300mL)After being added to the flask, the mixture was stirred at 120 C for 12 hours. After the reaction is complete,The mixture was filtered, washed with methanol, and filtered through a column. Then, the solvent was removed under reduced pressure,Recrystallized from EA / methanol to give compound 5-1(14g, 52%).
With copper(l) iodide; sodium t-butanolate; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 100℃; for 12h;
24 g (72 mmol) of Intermediate I-16-1, 24 g (86 mmol) of 1-bromo-3-iodobenzene, 0.685 g (3.6 mmol) of copper iodide, 13.83 g (143.96 mmol) of sodium tert-butoxide, 1.644 g (14.40 mmol) of trans-1,2-diaminocyclohexane, and 150 ml of dioxane were allowed to react at a temperature of 100 C. for 12 hours. After the reaction mixture was cooled to room temperature, ethanol was added thereto to produce precipitates that were subsequently separated by filtration. The separated precipitates were purified using column chromatography, thereby obtaining 26.4 g (yield: 75%) of Intermediate I-16-2.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;
The intermediate I-1 (20 g, 71 mmol) was dissolved in THF (1 L) in a nitrogen environment, 1-bromo-3-iodobenzene (24 g, 85 mmol) and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (0.8 mg, 0.7 mmol) were added thereto, and the mixture was stirred. Potassium carbonate (K2CO3) (24.5 g, 177 mmol) saturated in water was added thereto, and the resulting mixture was heated and refluxed at 80 C. for 12 hours. When the reaction was complete, water was added to the reaction solution, dichloromethane (DCM) was used for extraction, and an extract therefrom was treated with anhydrous MgSO4 to remove moisture, filtered, and concentrated under a reduced pressure. The obtained residue was separated and purified through flash column chromatography to obtain an intermediate I-2 (30 g and 90%). HRMS (70 eV, EI+): m/z calcd for C18H13Br: 309.1998, found 309 Elemental Analysis: C, 70%; H, 4%
90%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;
Synthesis of Intermediate I-2 (0237) The intermediate I-1 (20 g, 71 mmol) was dissolved in THF (1 L) in a nitrogen environment, 1-bromo-3-iodobenzene (24 g, 85 mmol) and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (0.8 mg, 0.7 mmol) were added thereto, and the mixture was stirred. Potassium carbonate (K2CO3) (24.5 g, 177 mmol) saturated in water was added thereto, and the resulting mixture was heated and refluxed at 80 C. for 12 hours. When the reaction was complete, water was added to the reaction solution, dichloromethane (DCM) was used for extraction, and an extract therefrom was treated with anhydrous MgSO4 to remove moisture, filtered, and concentrated under a reduced pressure. The obtained residue was separated and purified through flash column chromatography to obtain an intermediate I-2 (30 g and 90%). (0238) HRMS (70 eV, EI+): m/z calcd for C18H13Br: 309.1998, found: 309 Elemental Analysis: C, 70%; H, 4%
90%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;
Synthesis Example 38: Synthesis of Intermediate I-38 Compound I-37 (20 g, 71 mmol) was dissolved in THF (1 L) under a nitrogen environment, 1-bromo-3-iodobenzene (24 g, 85 mmol) and tetrakis(triphenylphosphine)palladium (0.8 mg, 0.7 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (24.5 g, 177 mmol) was added thereto, and the obtained mixture was heated and refluxed at 80 C. for 12 hours. When the reaction was complete, water was added to the reaction solution, and the mixture was extracted with dichloromethane (DCM) and then, filtered after removing moisture with anhydrous MgSO4 and concentrated under a reduced pressure. This obtained residue was separated and purified through flash column chromatography to obtain Compound I-38 (30 g and 90%). HRMS (70 eV, EI+): m/z calcd for C18H13Br:309.1998. found 309. Elemental Analysis: C, 70%; H, 4%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; for 6h;Inert atmosphere; Reflux;
3-Bromo-iodobenzene (17.6 g, 62 mmol) and naphthylphenyl boronic acid 3 (14.0 g, 62.1 mmol) Was dissolved in a mixed solvent of 170 ml of toluene and 85 ml of ethanol, and 85 ml of 2 M sodium carbonate aqueous solution, 2 g of tetrakis (triphenylphosphine) palladium were added, and the mixture was reacted under reflux with stirring for 6 hours under a nitrogen stream It was. Toluene and water were added, the layers were separated, and purified by silica gel column chromatography to obtain 13.0 g of Compound 4.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;
A mixture of <strong>[57002-01-4](E)-(2-cyclohexylvinyl)boronic acid</strong> (0.657 g, 4.27 mmol), 1 -bromo-3- iodobenzene (0.518 mL, 4.06 mmol), tetrakis (0.235 g, 0.203 mmol), and sodium carbonate 10% wt. in water (12.93 g, 12.19 mmol) in 1 ,4-dioxane (20 mL) was stirred for 2.0 hours at 100C, the LCMS showed a complete reaction with a major product (the product did not show desired mass). After cooled to the room temperature, the mixture was diluted with water and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate. It was filtered and the filtrate was concentrated. The crude product was purified on the Combiflash eluting with 100% hexanes. The title compound was obtained as clear colorless oil (1 .0 g, 3.77 mmol, 93 % yield). 1H NMR (400 MHz, chloroform-d) delta ppm 1 .13 - 1 .41 (m, 5 H) 1 .71 (m, 1 H) 1 .80 (m, 4 H) 2.10 - 2.20 (m, 1 H) 6.16 - 6.25 (m, 1 H) 6.25 - 6.33 (m, 1 H) 7.12 - 7.21 (m, 1 H) 7.26 (d, J=7.78 Hz, 1 H) 7.32 (d, J=7.78 Hz, 1 H) 7.52 (s, 1 H).
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 105℃; for 24h;Inert atmosphere;
Synthesis of Intermediate 1-b (0210) 1-bromo-3-iodobenzene (2.06 g, 20 mmol), a pyridin-2-ylboronic acid (3.2 g, 26 mmol), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, (1.6 g, 1.4 mmol), and sodium carbonate (Na2CO3, 5.3 g, 50 mmol) were loaded into a flask, and 50 mL of toluene and a mixture of ethanol/H2O (15 mL/15 mL) were added thereto. The flask was purged with nitrogen, and the mixture was reacted at a temperature of 105° C. for 24 hours. The reaction product was cooled to room temperature, and subjected to an extraction process using EA and water, thereby obtaining an organic layer. The organic layer was dried by using magnesium sulfate (MgSO4) and then condensed. The resultant was subjected to column chromatography (hexane:EA=3:1 at a volumetric ratio), thereby completing the preparation of Intermediate 1-b (Yield=67percent).
With pyridine; cesium fluoride; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; Schlenk technique;
General procedure: An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinacolatodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere, freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5mmol), and pyridine (0.4 to 1 equiv) were added successively. The reaction mixture was heated to 105 C and stirred for 2 h under argon.
3-bromophenyl 4-methoxy-2-nitrophenyl selenoether[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With 1,10-Phenanthroline; oxygen; copper diacetate; potassium carbonate; In toluene; at 100℃; for 24h;
At room temperature, <strong>[33844-21-2]2-nitro-4-methoxybenzoic acid</strong> (0.4 mmol, 1 equiv), elemental selenium (1.2mmol, 3equiv), 3- bromo-iodobenzene (1.2mmol, 3equiv), Cu (OAc) 2 (0.04mmol), 1,10- phenanthroline (0.04 mmol), potassium carbonate (1.2mmol, 3equiv) and 2mL of toluene was added to the reaction tube, then filled with oxygen, and substituted three times, the reaction in an oxygen environment, the reaction was stirred 24h 100 temperature. By the end of the reaction was monitored by thin layer chromatography, the reaction mixture was cooled, filtered and then ethyl acetate was added, and then spin off the solvent, the product obtained was isolated by column chromatography (eluent: petroleum ether: diethyl ether = 98), the product is yellow liquid, yield 77%, by weight of the product is 119mg.
With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; at 165℃; for 24h;
15 g (45 mmol) of <strong>[1247053-55-9]5-phenyl-5,12-dihydroindolo[3,2-a]carbazole</strong>, 15.3 g (54 mmol) of 3-bromoiodobenzene, 4.3 g (22.6 mmol) of CuI, 12.5 g (90 mmol) of K2CO3, and 9.7 g (54 mmol) of 1,10-phenanthroline were added into a 250-ml RBF, and 180 ml of DMF was added thereto. The mixture was stirred at a temperature of 165 C. for 24 hours. The reaction mixture was cooled and washed by water, and a solid product was extracted by MC. The solid product was dried by MgSO4 and distilled under reduced pressure. 12.8 g (58%) of Intermediate 2 was obtained after performing silica column chromatography (MC:Hexane=1:4).
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 100℃; for 18h;Inert atmosphere;
Intermediate I-37 (90 g, 329 mmol) was dissolved in toluene (1.0 L) in a nitrogen atmosphere,Here, 1-bromo-3-iodobenzene purchased from the tokyo chemical industry(102 g, 362 mmol), tris (diphenylideneacetone) dipalladium (0) (9.04 g, 9.87 mmol) tris-tert butylphosphine (9.98 g, 49.4 mmol) and sodium tert-butoxide(37.9 g, 395 mmol) were successively added thereto, followed by heating at 100 for 18 hours to reflux. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM)The water was removed with MgSO4, filtered and concentrated under reduced pressure. The thus obtained residueFlash column chromatography to obtain Intermediate I-38 (95.8 g, 68%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water;Reflux;
General procedure: 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (29.5 g, 80 mmol) was dissolved in 360 mL of THF, bromo-3'-iodo-1,1'-biphenyl (30.16 g, 84 mmol), Pd(PPh3) 4 (2.8 g, 2.4 mmol)NaOH (9.6 g, 240 mmol) and 180 mL of water are added, and the mixture is refluxed with stirring. After the reaction was completed, the reaction mixture was extracted with ether and water. The organic layer was dried over MgSO 4 and concentrated. The resulting organic material was purified by silicagel column and recrystallized to obtain 26.56 g (70%) of the product. <strong>[1246669-45-3]9-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole</strong> (73.92 g, 200.2 mmol) was dissolved in 880 mL of THF in a round bottom flask after, 1-bromo-2-iodobenzene (85.0 g, 300.3 mmol), Pd(PPh3)4 (11.6 g, 10 mmol) Sub1(10) proceed in the same manner as the experimental method, 55.8 g(Yield:70%) of Sub 1(5) was obtained.
With bis(eta3-allyl-mu-chloropalladium(II)); silver trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 100℃; under 3040.2 Torr; for 24h;Inert atmosphere; Sealed tube; Glovebox; Schlenk technique; Green chemistry;
General procedure: Under an inert nitrogen atmosphere, silver triflate (386 mg,1.5 mmol) was transferred to a Teflon sealed thick-walled 50 ml glass reaction vessel equipped with a stir bar, followed by aryl iodide (1.0 mmol), arene (2.0 mmol), DCE (4 ml) and then a freshly prepared stock solution of [Pd(allyl)Cl]2 (0.2 mg, 5 × 10-4 mmol). The vessel was closed, removed from the glovebox, evacuated and backfilled with carbon monoxide three times, and finally pressurized with 4 atm carbon monoxide. After heating at 100 C for 24 h with stirring, the reaction was cooled to room temperature and carbon monoxide was released. The reaction mixture was filtered through Celite, eluting with dichloromethane. Saturated NaHCO3 was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were concentrated in vacuo and the residue was purified by column chromatography (silica gel, gradient hexane/ethyl acetate 0 to 20%) to afford the pure ketone product.
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 15h;Inert atmosphere;
Under a nitrogen atmosphere (N2 purging), Compound 1G(10 g, 35.48 mmol), 0.6 equivalent of Compound 3A, 0.1 equivalent of CuI, 3.5 equivalents of diaminocyclohexane, and 4.0 equivalents of potassium phosphate were added to 1,4-dioxane(350 ml), and stirred in a 90 C. oil bath. After 15 hours, water was added to the reaction mixture, and extraction was performed. Then, purification was performed using a column using a developing solvent of hexane: MC (3:2) to obtain a white solid 3B(12.93 g. yield 75%).
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 12h;
In a nitrogen environment and (N2 purging) 5A,0.6 equivalent of 2A, 0.1 equivalent of CuI,3.5 equivalents of diaminocyclohexane,4.0 equivalents of potassium phosphate are added to 1,4-dioxane and stirred in an oil bath at 90 C. Water was added to the reaction mixture after 12 hours, and after extraction with hexane: MC (4: 1) developing solvent, white solid 6A was obtained.
With tetrakis(triphenylphosphine) palladium(0); silver carbonate; In tetrahydrofuran; at 100℃; for 12h;Sealed tube;
Boronate ester (2.00 g, 5.40 mmol), 3-Bromoiodobenzene (1.38 mL, 10.8 mmol),Tetrakis (triphenylphosphine) palladium (0) (0.630 g, 0.540 mmol), Ag 2 CO 3 (2.99 g, 10.8 mmol) and 90 mL of tetrahydrofuran were placed in a 150 mL medium pressure vessel.The mixture was heated and stirred for 12 hours at 100 .The reaction solution was cooled to room temperature,Filtered through celite.The filtrate was concentrated in vacuo,The residue was purified by column chromatography (Hexane: Toluene = 4: 1)Thus,43-2 (9- (3'-bromo- [1,1'-biphenyl] -3-yl) -9H-carbazole) (1.61 g, 75% yield).
tert-butyl 2-(3-bromophenyl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃;Sealed tube; Inert atmosphere;
in a sealable reaction tube was mixed 1-brorno-3-iodobenzene (445 mg, 1.573mmol), tert-hutyl i-oxo-2,8-diazaspiro[4.5]decane-8-carboxyiate (200 rng, 0.786 mmol),Cesium carbonate (512 rng, 1.573 rnmol) and dioxane (1573 pi). The reaction was purged with N2. Then 9.9-Dimethyl-4,5--bis(diphenyiphosphino)xanthene (68.3 mg, 0.118 mmol), Pd2(dha)3 (36.0 mg, 0.039 mmol)was added and N2 was bubbled through reaction for I mm, The reaction was sealed and stirred at 100 C overnight. The reactionwas partitioned between EtOAc(50 ml) and water (30 ml). The organic layer was separated, washed with water (2 x 30 ml) and brine (30 ml). dried over MgSO4, filtered and concentrated. The residue was purified using ISCO system (0-100% EtOAc/Hex gradient) to give tert-butyl 2-(3-brornophenyl)- I -oxo-2,8-diazaspiro[4. 5Idecane-8- carboxylate (300 rng, 0.733 mrnoi, 93 % yield) as a beige solid. ?H NMR (500MHz.DMSO-d6) 8,13 7.93 (m, 11:1), 7.61 (dt,J=6.7. 2.3 Hz, 11-i), 7.42- 724 (m. 2H). 3.93-3.74 (m. 4H), 309 - 2.82 (m, 2H), 2.09 (t, J=7.0 Hz, 2H), 1.62 (td, J=12.4, 4,1 Hz, 2H),1.55 - 146 (m, 2H), 1.42 (s, 9H); MS (ES) ith: 409.0, 411.0 (M-l-H)1.
7-(3-bromophenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-amine[ No CAS ]
7-(3-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
<strong>[84955-31-7]4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong> (500 mg, 2.97 mmol) and ammonium formate (630 mg, 9mmol) were added to the eggplant flask, and 20 mL of isopropanol was added to the reaction solution. Inaddition to oxygen. Palladium on carbon (10% Pd, 306 mg) was added, and the reaction solution was evaporatedto reflux and stirred overnight. After completion of the reaction, the mixture was cooled to room temperature,filtered, washed with methanol, and the filtrate was concentrated on a rotary evaporator to give 270 mg of crudeproduct (the ratio of the two products: 1:1). Used directly in the next step.E21 (270 mg, 2.01 mmol), 1-bromo-3-iodobenzene (1128 mg, 4.00 mmol), potassium carbonate (828 mg, 6.00mmol) and proline(46 mg, 0.40 mmol) were added to the eggplant flask and added dimethyl sulfoxide, thereaction solution removes oxygen. Copper iodide (38 mg, 0.20 mmol) was added and the reaction solution wasdeoxygenated. Heat to 90 C and stir for 16 hours. After the reaction was completed, it was cooled to roomtemperature, water and ethyl acetate were added, and the mixture was filtered over celite. The target compoundwas obtained in 50 mg.
7-(3-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
229 mg
With copper(l) iodide; potassium carbonate; rac-Pro-OH; In dimethyl sulfoxide; at 90℃; for 16.0h;
<strong>[93366-88-2]7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong> (268 mg, 2 mmol), 1-bromo-3-iodobenzene (1120 mg, 4 mmol),potassium carbonate (828 mg, 6 mmol) and proline(46 mg) , 0.4 mmol) was added to an eggplant type flask,dimethyl sulfoxide was added, and the reaction solution was deoxidized. Copper iodide (40 mg, 0.2 mmol) wasadded and the reaction solution was deoxygenated. Heat to 90 C and stir for 16 hours. After the reaction wascompleted, it was cooled to room temperature, water and ethyl acetate were added, and the mixture was filteredover Celite. The target compound was obtained in 229 mg.
229 mg
With copper(l) iodide; potassium carbonate; rac-Pro-OH; In dimethyl sulfoxide; at 90℃; for 16.0h;
<strong>[93366-88-2]7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong> (268 mg, 2 mmol), 1-bromo-3-iodobenzene (1120 mg, 4 mmol),potassium carbonate (828 mg, 6 mmol) and proline (46 mg) , 0.4 mmol) was added to an eggplant type flask,dimethyl sulfoxide was added, and the reaction solution was deoxidized. Copper iodide (40 mg, 0.2 mmol) wasadded and the reaction solution was deoxygenated. Heat to 90C and stir for 16 hours. After the reaction was completed, it was cooled to room temperature, water and ethyl acetate were added, and the mixture was filtered over Celite. The target compound was obtained in 229 mg.
With copper(l) iodide; potassium carbonate; rac-Pro-OH; In dimethyl sulfoxide; at 90℃; for 16h;
Add <strong>[452-06-2]9H-purin-2-amine</strong> (200 mg, 1.48 mmol), 1-bromo-3-iodobenzene (849 mg, 3 mmol), potassium carbonate(621 mg, 4.5 mmol) and proline (35 mg, 0.3 mmol) to the eggplant In the flask, dimethyl sulfoxide was added, and the reaction solution was deoxidized. Copper iodide (29 mg, 0.15 mmol) was added and the reaction solution was deoxygenated. Heat to 90 C and stir for 16 hours. After the reaction was completed, it was cooled to room temperature, water and ethyl acetate were added, and the mixture was filtered over celite. The target compound was obtained in an amount of 250 mg.
methyl 1-(3-bromophenylazetidine)-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; XPhos; In 1,4-dioxane; at 100℃;
To a solution of 1 -bromo-3-iodobenzene (500 mg, 1.77 mmol) in dioxane (8 mL) was added <strong>[100202-39-9]methyl azetidine-3-carboxylate hydrochloride</strong> (295 mg, 1 .94 mol), Pd2(dba)3 (35 mg, 40 pmol), XPhos (17 mg, 40 pmol) and Na2C03 (375 mg, 3.53 mmol). The mixture was stirred at 100C overnight, cooled to rt, filtered, concentrated and purified by prep-TLC (PE:EA = 2:1 ) to give compound P12 as a yellow oil.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
