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CAS No. : | 955959-84-9 | MDL No. : | MFCD19441306 |
Formula : | C18H11BrO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | RIPZSADLUWTEFQ-UHFFFAOYSA-N |
M.W : | 323.18 | Pubchem ID : | 59022098 |
Synonyms : |
|
Num. heavy atoms : | 20 |
Num. arom. heavy atoms : | 19 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 86.86 |
TPSA : | 13.14 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.03 cm/s |
Log Po/w (iLOGP) : | 3.41 |
Log Po/w (XLOGP3) : | 5.98 |
Log Po/w (WLOGP) : | 6.02 |
Log Po/w (MLOGP) : | 4.74 |
Log Po/w (SILICOS-IT) : | 5.65 |
Consensus Log Po/w : | 5.16 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 1.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -6.25 |
Solubility : | 0.000183 mg/ml ; 0.000000565 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -6.03 |
Solubility : | 0.0003 mg/ml ; 0.000000928 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -8.31 |
Solubility : | 0.00000159 mg/ml ; 0.0000000049 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.73 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 8 h; Inert atmosphere | In a nitrogen atmosphere, dibenzofuran-4-ylboronic acid (100 g, 472 mmol) was dissolved in 1,000 mL of tetrahydrofuran (THF)1-bromo-4-iodobenzene (160 g, 556 mmol) and tetrakis (triphenylphosphine) palladium (5.45 g, 4.72 mmol) were added thereto and stirred.Potassium carbonate (78.3 g, 566 mmol) saturated with water was added and the mixture was refluxed by heating at 80 ° C for 8 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM). Then, water was removed with anhydrous MgSO 4,Filtered and concentrated under reduced pressure.The thus-obtained residue was purified by flash column chromatography to obtain Compound I-9 (142 g, 93percent). |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 12 h; Reflux; Inert atmosphere | To a round bottom flask, 4-dibenzofuran boronic acid 20g (94.3mmol), 1- bromo-4-iodo benzene 26.7g (94.3mmol) was put and toluene (313ml) mmol) was added and dissolved and then an aqueous solution 117ml of potassium carbonate 19.5g (141.5 mmol)dissolved was added and stirred. Here, tetrakis triphenylphosphine palladium 1.09g (0.94mmol)was added and stirred under reflux for 12 hours under a nitrogen atmosphere.After the end of the reaction and the extract was extracted to ethyl acetate, the extract was dried and filtered through magnesium sulfate, and the filtrate was concentrated under reduced pressure.The product n- hexane / dichloromethane (9: 1 volumetric ratio) was purified by silica gel column chromatography to give the 27g (89percentyield) of the aimed compound intermediate M-1 as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 12 h; Inert atmosphere; Reflux | 4-dibenzofuran boronic acid 20g (94.3mmol) in a round bottom flask, 1-bromo-4-iodo benzene, 26.7g (94.3mmol) And stirred into 117ml aqueous solution was added to dissolve the potassium carbonate and 19.5g (141.5mmol) was dissolved was added to toluene (313ml). Followed by adding thereto tetrakis triphenylphosphine palladium 1.09g (0.94mmol) was stirred under reflux for 12 hours under a nitrogen atmosphere. After the end of the reaction the extract was concentrated to dryness and extracted with ethyl acetate and filtered through a magnesium sulfate, and the filtrate under reduced pressure. The product n- hexane / dichloromethane (9: 1 by volume) was purified by a silica gel column chromatography to give the intermediate M-1 as a white solid 27g (89percent yield). |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 12 h; Reflux; Inert atmosphere | 4-dibenzofuran boronic acid 20g (94.3mmol) and 1-bromo-4-iodo benzene 26.7g(94.3mmol) in toluene (313 ml) was added in a round bottom flask and stirred, an aqueous solution (117 ml) of potassium carbonate 19.5g (141.5mmol) was added, followed by adding tetrakistriphenylphosphine palladium 1.09g (0.94mmol) and stirred under reflux for 12 hours under a nitrogen atmosphere. After the end of the reaction, the reaction mixture was extracted with ethyl acetate, dried using magnesium sulfate, and the filtrate was concentrated under reduced pressure. The obtained product was purified by silica gel column chromatography using n-hexane/dichloromethane (9: 1 by volume) to give the desired intermediate compound M-1 27g (89percent yield) as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene for 12 h; Inert atmosphere; Reflux | 4-benzofuran boronic acid (4-dibenzofuranboronic acid) 20g (94.4mmol), 1- bromo-4-iodo-benzene 28g (99.2mmol) and tetrakistriphenylphosphine palladium flask 1.08g (0.94mmol) put in was dissolved in 240ml of toluene and 120mL of ethanol under a nitrogen atmosphere after the addition of an aqueous solution of potassium carbonate dissolved in 120ml 28g (188.8mmol) it was stirred under reflux for 12 hours. After the reaction the extract was dried, filtered and then extracted with ethyl acetate and with magnesium sulfite and concentrated under reduced pressure of the filtrate. The product n- hexane / dichloromethane (9: 1 by volume) as the desired compound of intermediate M-9 was purified by silica gel column chromatography to give a 27g (89percent yield) as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 12 h; Inert atmosphere; Reflux | Will be 20 grams (94.3 millimoles) 4-dibenzofuran boric acid and 26.7 g (94.3 mmol) 1-Bromo-4-iodobenzene was placed in a round bottom flask, and 313 ml of toluene was added thereto to dissolve it. A 117 ml aqueous solution obtained by dissolving 19.5 g (141.5 mmol) of potassium carbonate was added thereto, and the mixture was agitated. Subsequently, 1.09 g (0.94 mmol) of tetratriphenylphosphine palladium was added thereto. The resulting mixture was refluxed under a nitrogen atmosphere and stirred for 12 hours. When the reaction was completed, the resultant was extracted with ethyl acetate. The extracted solution was dried over magnesium sulfate and filtered. The filtered solution was concentrated under reduced pressure. Subsequently, the product obtained therefrom was treated with n-hexane/dichloromethane (9:1 vol/vol) Purified by gel column chromatography, Obtained 27 g of intermediate M-1 as a white solid (yield: 89percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene for 10 h; Inert atmosphere; Reflux | [Production Example 1] Synthesis of 4-(4-bromophenyl)dibenzofuran Under an argon atmosphere, 300 mL of toluene and 150 mL of a 2-M aqueous solution of sodium carbonate were added to 28.3 g (100 mmol) of 4-iodobromobenzene, 22.3 g (105 mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of tetrakis(triphenylphosphine)palladium(0), and the mixture was refluxed under heat for 10 hours. Immediately after the completion of the reaction, the resultant was filtrated, and then the water layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography, whereby 26.2 g of the white crystal of 4-(4-bromophenyl)dibenzofuran were obtained (81percent yield). |
81% | With sodium carbonate In water; toluene for 10 h; Reflux; Inert atmosphere | <Synthesis Example 5 (Synthesis of Intermediate 5)>; Under the atmosphere of argon gas, 300 ml of toluene and 150 ml of 2 M concentration sodium carbonate aqueous solution was added to 28.3 g (100 mmol) of 4-iodobromobenzene, 22.3 g (105 mmol) of dibenzofurazi-4-boronic acid and 2.31 g (2. 00 mmol) of tetrakis(triphenylphosphine)palladium (0), and the resultant mixture solution was heated while refluxing for 10 hours. After the reaction was completed, filtration was carried out immediately and a water layer was removed. After drying the organic layer over sodium sulfate, the resultant was concentrated. The residue was subjected to a chromatography purification using a silica gel column to obtain 26.2 g of 4-(4-bromophenyl)dibenzofuriran in the state of a white crystal (yield:81percent). The resultant white crystal was identified as Intermediate 5 from the result in accordance with the FD-MS analysis. |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | In an argon atmosphere, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3 were added to a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid and 2.31 g (2.00 mmol) of Pd[PPh3]4, and the resultant mixture was stirred for 10 h while refluxing under heating. [0160] After the reaction, the reaction product extracted with dichloromethane in a separatory funnel. The organic layer was dried over MgSO4, filtered, and then concentrated. The concentrate was purified by silica gel column chromatography, to obtain 26.2 g of a white solid, which was identified as the following intermediate 1-5 by FD-MS analysis (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | [0184] In an argon atmosphere, 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid and 2.31 g (2.00 mmol) of Pd[PPh3]4 were added with 150 ml of toluene, 150 ml of dimethoxyethane and150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3. The resultant mixture was stirred for 10 h while refluxingunder heating.[0185] After the reaction, the mixture was extracted with dichloromethane in a separatory funnel. The organic layerwas dried over MgSO4, filtered, and then concentrated. The concentrate was purified by silica gel column chromatographyto obtain 26.2 g of white solid, which was identified as the following intermediate 1-4 by FD-MS (yield: 81percent) |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | INTERMEDIATE SYNTHESIS 1-1 (Synthesis of intermediate 1-1) [0106] Under an argon atmosphere, into a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of Pd[PPh3]4, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3 were added, and the resultant mixture was stirred for 10 h while refluxing under heating. [0107] After the reaction, the obtained mixture was cooled to room temperature and extracted with dichloromethane in a separatory funnel. The organic layer was dried over MgSO4, and then filtered and condensed. The condensate was purified by silica gel column chromatography to obtain 26.2 g of a white solid, which was identified as the intermediate 1-1 by FD-MS analysis (Field Desorption Mass Spectrometry Analysis) (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | INTERMEDIATE SYNTHESIS 2-1 (Synthesis of intermediate 2-1)[0105] Under an argon atmosphere, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2M aqueous solution of Na2CO3 were added to a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of Pd[PPh3]4, and the resultant mixture was stirred for10 h while refluxing under heating.[0106] After the reaction, the obtained mixture was cooled to room temperature and extracted with dichloromethanein a separatory funnel. The organic layer was dried over MgSO4, and then filtered and concentrated. The concentratewas purified by silica gel column chromatography to obtain 26.2 g of a white solid, which was identified as the intermediate2-1 by FD-MS analysis (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | In the argon atmosphere, are respectively weighing 4-iodo-bromobenzene 28.3g (100.0mmol), dibenzofuran-4-boronic acid 22.3g (105.0mmol), Pd[PPh3]42.31g (2.00mmol), adding toluene 150 ml, dimethoxy ethane 150 ml and 2M the Na2CO3aqueous solution 150 ml (300.0mmol), heating to reflux stirring 10 hours.After the reaction, cooling to room temperature, the reaction mixture is transferred to the separatory funnel, using dichloromethane extract. The organic layer using MgSO4dried, filtered and concentrated. The concentrated residue is purified with silica gel column chromatography, thereby obtaining 26.2g white solid (yield 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water; toluene for 10 h; Inert atmosphere; Reflux | Under an argon atmosphere, toluene (150 mL), dimethoxyethane (150 mL), and an aqueous solution of sodium carbonate having a concentration of 2 M (150 mL) were added to 4-iodobromobenzene (28.3 g, 100.0 mmol), dibenzofuran-4-boronic acid (22.3 g, 105 mmol), and tetrakis(triphenylphosphine)palladium(0) (2.31 g, 2.00 mmol), and then the mixture was heated for 10 hours while being refluxed. Immediately after the completion of the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, an intermediate body 3H-1 (26.2 g, 81percent yield) was obtained. FD-MS (field desorption mass spectrometry) analysis confirmed that the intermediate had a ratio m/e of 322 with respect to its molecular weight, i.e., 322. |
81% | Stage #1: With sodium carbonate In toluene for 0.333333 h; Stage #2: With tetrakis(triphenylphosphine) palladium(0) In toluene for 4 h; Reflux |
To a round bottom flask was added dibenzofuran-4-boronic acid (1.6 g, 5 mmol),4-iodobromobenzene (1.35 g, 4.76 mmol), sodium carbonate (1.48 g, 2M)toluene (50 ml) was added thereto, followed by stirring for 20 minutes. Tetrakis (triphenylphosphine) palladium (0) (0.11 g, 0.095 mmol) was added and the mixture was refluxed for 4 hours.After confirming with HPLC and LC-MASS, the reaction was terminated. After removal of the solvent, it was extracted with MC / H2O. column (MC: Hex = 1: 4) and reprecipitated with MC / hexane to obtain a solid compound (1.24 g, yield = 81percent). |
56% | With potassium carbonate In ethanol; water; toluene at 70 - 80℃; for 3 h; | Preparation of compound C-6-1 [133] After dissolving dibenzo[b,d]furan-4-yl boronic acid (20 g, 94.34 mmol), 1-bromo-4-iodo-benzene (53.4 ml, 188.68 mmol), Pd(PPh3)4 (5.45 g, 4.72 mmol) and K2CO3 (39.1 g, 283.01 mmol) in a mixture of toluene (900mL), EtOH (200mL) and distilled water (200mL), the reaction mixture was stirred for 3 hours at 70~80°C. After terminating the reaction, an aqueous layer was removed from the mixture by a gravity separation. And then, the obtained organic layer was concentrated and purified through column to obtain compound C-6-1 (17 g, 56 percent). |
28.5 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In toluene at 80℃; for 8 h; Inert atmosphere | A three neck flask of 1000 ml was charged with 42.4 g of 4-dibenzofuranboronic acid, 56.0 g of 4-iodobromobenzene, 6.9 g of tetrakis-(triphenylphosphine)palladium (Pd(PPh3)4), 320 mL of a sodium carbonate (Na2CO3) solution of 2M and 320 mL of toluene under argon flow, and then they were reacted at 80° C. for 8 hours. The reaction solution was extracted with toluene/water, and the extract was dried on anhydrous sodium sulfate. This was concentrated under reduced pressure, and a crude product obtained was refined through a column, whereby 28.5 g of a white powder was obtained. |
27 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene for 12 h; Inert atmosphere | 20 g (94.4 mmol) of 4-dibenzofuranboronic acid, 28 g (99.2 mmol) of 1-bromo-4-iodobenzene, and 1.08 g (0.94 mmol) of tetrakistriphenylphosphine palladium were dissolved in 240 ml of toluene and 120 ml of ethanol under a nitrogen atmosphere in a flask, 120 ml of an aqueous solution in which 28 g (188.8 mmol) of potassium carbonate was dissolved was added thereto, and the mixture was agitated for 12 hours while being refluxed. When the reaction was complete, the resultant was extracted with ethyl acetate, the extracted solution was dried with magnesium sulfite and filtered, and the filtered solution was concentrated under a reduced pressure. The concentrated product was purified with n-hexane/dichloromethane (9:1 of a volume ratio) through silica gel column chromatography, obtaining 27 g of a white solid compound, an intermediate M-9 (89percent of a yield). |
5.92 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 100℃; for 24 h; | In the 250 mE rounded-bottom flask, the compoundF 1(3.00 g, 14.15 mmol), the compoundA4 (4.00 g, 14.15mmol), tetrakis(triphenylphosphine)palladium(0) (0.82 g,0.71 mmol) and potassium carbonate (4.84 g, 35.00 mmol)were put into a mixture of toluene (70 mE), ethanol (35 mE)and water (17.5 mE) and stirred under the temperature of100° C. for 24 irs. Afier the completion of the reaction, the mixture was extracted and condensed using water and dichloromethane. The mixture was separated by a column using dichloromethane and n-hexane and precipitated using dichloromethane and petroleum ether. The precipitate was filtered such that the compound F2 was obtained. (5.92 g, 25.29 mmol) |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 100℃; for 24 h; | To a 250 mL round bottom flask was added G1 (3.00 g, 14.15 mmol),G2 (4.00 g, 14.15 mmol), tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol) and potassium carbonate (4.84 g, 35.00 mmol) were dissolved in toluene (80 mL) Ethanol (20 mL) and water (20 mL) were added to the mixed solution,And the mixture was stirred at 100 DEG C for 24 hours. After completion of the reaction,Water and dichloromethane were used for extraction and concentration,The column was separated using dichloromethane and n-hexane.Then, the precipitate was prepared by using dichloromethane and petroleum ether, Filtration gave Compound G3 (3.95 g, 12.22 mmol). |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 100℃; for 24 h; | Dibenzofuran-4-boronic acid (3.00 g, 14.15 mmol), 1-bromo-4-iodobenzene (4.00 g, 14.15 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol) in a 250 mL round- and potassium carbonate (4.84 g, 35.00 mmol) were added to a mixed solution of Toluene (80 mL), Ethanol (20 mL) and water (20 mL) and stirred at 100 ° C for 24 hours. After completion of the reaction, the reaction mixture was extracted with water and dichloromethane, concentrated, and then subjected to column separation using dichloromethane and n-hexane. Thereafter, a precipitate was prepared using dichloromethane and petroleum ether, and filtered to obtain Compound D1 (3.95 g, 12.22 mmol). |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 100℃; for 24 h; | Dibenzofuran-4-boronic acid (3.00 g, 14.15 mmol), 1-bromo-4-iodobenzene (4.00 g, 14.15 mmol), tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol)Potassium carbonate (4.84 g, 35.00 mmol) was dissolved in toluene (80 mL)Was added to a mixed solution of ethanol (20 mL) and water (20 mL), and the mixture was stirred at 100 ° C for 24 hours. After completion of the reaction, the reaction mixture was extracted with water and dichloromethane,The mixture was concentrated, and the column was separated using dichloromethane and n-hexane.Then, the precipitate was prepared by using dichloromethane and petroleum ether,Filtration gave Compound G1 (3.95 g, 12.22 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13.7 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 80℃; for 5 h; | At 80°C, 4-dibenzofuranboronic acid (13.3g), 1,4-dibromobenzene (10g), tetrakis(triphenylphosphine)palladium (3.02g), toluene (158mL), ethanol (65mL), water (65mL), and potassium carbonate (21.69g) were stirred for 5 hours. The reaction was monitored by thin layer chromatography. Upon completion of the reaction, it was quenched with water (100mL) and extracted with ethyl acetate (100mL). The organic layer was extracted with water (3x30mL) and dried over anhydrous sodium sulfate. The ethyl acetate layer was collected through Celite and further purified by column chromatography. Following this, the ethyl acetate layer was evaporated to dryness under vacuum rotavap to yield 13.7g 4-(4'-bromophenyl)dibenzofuran. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 8h;Inert atmosphere; | In a nitrogen atmosphere, dibenzofuran-4-ylboronic acid (100 g, 472 mmol) was dissolved in 1,000 mL of tetrahydrofuran (THF)1-bromo-4-iodobenzene (160 g, 556 mmol) and tetrakis (triphenylphosphine) palladium (5.45 g, 4.72 mmol) were added thereto and stirred.Potassium carbonate (78.3 g, 566 mmol) saturated with water was added and the mixture was refluxed by heating at 80 ° C for 8 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM). Then, water was removed with anhydrous MgSO 4,Filtered and concentrated under reduced pressure.The thus-obtained residue was purified by flash column chromatography to obtain Compound I-9 (142 g, 93percent). |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Reflux; Inert atmosphere; | To a round bottom flask, 4-dibenzofuran boronic acid 20g (94.3mmol), 1- bromo-4-iodo benzene 26.7g (94.3mmol) was put and toluene (313ml) mmol) was added and dissolved and then an aqueous solution 117ml of potassium carbonate 19.5g (141.5 mmol)dissolved was added and stirred. Here, tetrakis triphenylphosphine palladium 1.09g (0.94mmol)was added and stirred under reflux for 12 hours under a nitrogen atmosphere.After the end of the reaction and the extract was extracted to ethyl acetate, the extract was dried and filtered through magnesium sulfate, and the filtrate was concentrated under reduced pressure.The product n- hexane / dichloromethane (9: 1 volumetric ratio) was purified by silica gel column chromatography to give the 27g (89percentyield) of the aimed compound intermediate M-1 as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Inert atmosphere; Reflux; | 4-dibenzofuran boronic acid 20g (94.3mmol) in a round bottom flask, 1-bromo-4-iodo benzene, 26.7g (94.3mmol) And stirred into 117ml aqueous solution was added to dissolve the potassium carbonate and 19.5g (141.5mmol) was dissolved was added to toluene (313ml). Followed by adding thereto tetrakis triphenylphosphine palladium 1.09g (0.94mmol) was stirred under reflux for 12 hours under a nitrogen atmosphere. After the end of the reaction the extract was concentrated to dryness and extracted with ethyl acetate and filtered through a magnesium sulfate, and the filtrate under reduced pressure. The product n- hexane / dichloromethane (9: 1 by volume) was purified by a silica gel column chromatography to give the intermediate M-1 as a white solid 27g (89percent yield). |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Reflux; Inert atmosphere; | 4-dibenzofuran boronic acid 20g (94.3mmol) and 1-bromo-4-iodo benzene 26.7g(94.3mmol) in toluene (313 ml) was added in a round bottom flask and stirred, an aqueous solution (117 ml) of potassium carbonate 19.5g (141.5mmol) was added, followed by adding tetrakistriphenylphosphine palladium 1.09g (0.94mmol) and stirred under reflux for 12 hours under a nitrogen atmosphere. After the end of the reaction, the reaction mixture was extracted with ethyl acetate, dried using magnesium sulfate, and the filtrate was concentrated under reduced pressure. The obtained product was purified by silica gel column chromatography using n-hexane/dichloromethane (9: 1 by volume) to give the desired intermediate compound M-1 27g (89percent yield) as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; for 12h;Inert atmosphere; Reflux; | 4-benzofuran boronic acid (4-dibenzofuranboronic acid) 20g (94.4mmol), 1- bromo-4-iodo-benzene 28g (99.2mmol) and tetrakistriphenylphosphine palladium flask 1.08g (0.94mmol) put in was dissolved in 240ml of toluene and 120mL of ethanol under a nitrogen atmosphere after the addition of an aqueous solution of potassium carbonate dissolved in 120ml 28g (188.8mmol) it was stirred under reflux for 12 hours. After the reaction the extract was dried, filtered and then extracted with ethyl acetate and with magnesium sulfite and concentrated under reduced pressure of the filtrate. The product n- hexane / dichloromethane (9: 1 by volume) as the desired compound of intermediate M-9 was purified by silica gel column chromatography to give a 27g (89percent yield) as a white solid. |
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Inert atmosphere; Reflux; | Will be 20 grams (94.3 millimoles) 4-dibenzofuran boric acid and 26.7 g (94.3 mmol) 1-Bromo-4-iodobenzene was placed in a round bottom flask, and 313 ml of toluene was added thereto to dissolve it. A 117 ml aqueous solution obtained by dissolving 19.5 g (141.5 mmol) of potassium carbonate was added thereto, and the mixture was agitated. Subsequently, 1.09 g (0.94 mmol) of tetratriphenylphosphine palladium was added thereto. The resulting mixture was refluxed under a nitrogen atmosphere and stirred for 12 hours. When the reaction was completed, the resultant was extracted with ethyl acetate. The extracted solution was dried over magnesium sulfate and filtered. The filtered solution was concentrated under reduced pressure. Subsequently, the product obtained therefrom was treated with n-hexane/dichloromethane (9:1 vol/vol) Purified by gel column chromatography, Obtained 27 g of intermediate M-1 as a white solid (yield: 89percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; toluene; for 10h;Inert atmosphere; Reflux; | [Production Example 1] Synthesis of 4-(4-bromophenyl)dibenzofuran Under an argon atmosphere, 300 mL of toluene and 150 mL of a 2-M aqueous solution of sodium carbonate were added to 28.3 g (100 mmol) of 4-iodobromobenzene, 22.3 g (105 mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of tetrakis(triphenylphosphine)palladium(0), and the mixture was refluxed under heat for 10 hours. Immediately after the completion of the reaction, the resultant was filtrated, and then the water layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography, whereby 26.2 g of the white crystal of 4-(4-bromophenyl)dibenzofuran were obtained (81percent yield). |
81% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 10h;Reflux; Inert atmosphere; | <Synthesis Example 5 (Synthesis of Intermediate 5)>; Under the atmosphere of argon gas, 300 ml of toluene and 150 ml of 2 M concentration sodium carbonate aqueous solution was added to 28.3 g (100 mmol) of 4-iodobromobenzene, 22.3 g (105 mmol) of dibenzofurazi-4-boronic acid and 2.31 g (2. 00 mmol) of tetrakis(triphenylphosphine)palladium (0), and the resultant mixture solution was heated while refluxing for 10 hours. After the reaction was completed, filtration was carried out immediately and a water layer was removed. After drying the organic layer over sodium sulfate, the resultant was concentrated. The residue was subjected to a chromatography purification using a silica gel column to obtain 26.2 g of 4-(4-bromophenyl)dibenzofuriran in the state of a white crystal (yield:81percent). The resultant white crystal was identified as Intermediate 5 from the result in accordance with the FD-MS analysis. |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | In an argon atmosphere, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3 were added to a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid and 2.31 g (2.00 mmol) of Pd[PPh3]4, and the resultant mixture was stirred for 10 h while refluxing under heating. [0160] After the reaction, the reaction product extracted with dichloromethane in a separatory funnel. The organic layer was dried over MgSO4, filtered, and then concentrated. The concentrate was purified by silica gel column chromatography, to obtain 26.2 g of a white solid, which was identified as the following intermediate 1-5 by FD-MS analysis (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | [0184] In an argon atmosphere, 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid and 2.31 g (2.00 mmol) of Pd[PPh3]4 were added with 150 ml of toluene, 150 ml of dimethoxyethane and150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3. The resultant mixture was stirred for 10 h while refluxingunder heating.[0185] After the reaction, the mixture was extracted with dichloromethane in a separatory funnel. The organic layerwas dried over MgSO4, filtered, and then concentrated. The concentrate was purified by silica gel column chromatographyto obtain 26.2 g of white solid, which was identified as the following intermediate 1-4 by FD-MS (yield: 81percent) |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | INTERMEDIATE SYNTHESIS 1-1 (Synthesis of intermediate 1-1) [0106] Under an argon atmosphere, into a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of Pd[PPh3]4, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2 M aqueous solution of Na2CO3 were added, and the resultant mixture was stirred for 10 h while refluxing under heating. [0107] After the reaction, the obtained mixture was cooled to room temperature and extracted with dichloromethane in a separatory funnel. The organic layer was dried over MgSO4, and then filtered and condensed. The condensate was purified by silica gel column chromatography to obtain 26.2 g of a white solid, which was identified as the intermediate 1-1 by FD-MS analysis (Field Desorption Mass Spectrometry Analysis) (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | INTERMEDIATE SYNTHESIS 2-1 (Synthesis of intermediate 2-1)[0105] Under an argon atmosphere, 150 ml of toluene, 150 ml of dimethoxyethane, and 150 ml (300.0 mmol) of a 2M aqueous solution of Na2CO3 were added to a mixture of 28.3 g (100.0 mmol) of 4-iodobromobenzene, 22.3 g (105.0mmol) of dibenzofuran-4-boronic acid, and 2.31 g (2.00 mmol) of Pd[PPh3]4, and the resultant mixture was stirred for10 h while refluxing under heating.[0106] After the reaction, the obtained mixture was cooled to room temperature and extracted with dichloromethanein a separatory funnel. The organic layer was dried over MgSO4, and then filtered and concentrated. The concentratewas purified by silica gel column chromatography to obtain 26.2 g of a white solid, which was identified as the intermediate2-1 by FD-MS analysis (yield: 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | In the argon atmosphere, are respectively weighing 4-iodo-bromobenzene 28.3g (100.0mmol), dibenzofuran-4-boronic acid 22.3g (105.0mmol), Pd[PPh3]42.31g (2.00mmol), adding toluene 150 ml, dimethoxy ethane 150 ml and 2M the Na2CO3aqueous solution 150 ml (300.0mmol), heating to reflux stirring 10 hours.After the reaction, cooling to room temperature, the reaction mixture is transferred to the separatory funnel, using dichloromethane extract. The organic layer using MgSO4dried, filtered and concentrated. The concentrated residue is purified with silica gel column chromatography, thereby obtaining 26.2g white solid (yield 81percent). |
81% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | Under an argon atmosphere, toluene (150 mL), dimethoxyethane (150 mL), and an aqueous solution of sodium carbonate having a concentration of 2 M (150 mL) were added to 4-iodobromobenzene (28.3 g, 100.0 mmol), dibenzofuran-4-boronic acid (22.3 g, 105 mmol), and tetrakis(triphenylphosphine)palladium(0) (2.31 g, 2.00 mmol), and then the mixture was heated for 10 hours while being refluxed. Immediately after the completion of the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, an intermediate body 3H-1 (26.2 g, 81percent yield) was obtained. FD-MS (field desorption mass spectrometry) analysis confirmed that the intermediate had a ratio m/e of 322 with respect to its molecular weight, i.e., 322. |
81% | To a round bottom flask was added dibenzofuran-4-boronic acid (1.6 g, 5 mmol),4-iodobromobenzene (1.35 g, 4.76 mmol), sodium carbonate (1.48 g, 2M)toluene (50 ml) was added thereto, followed by stirring for 20 minutes. Tetrakis (triphenylphosphine) palladium (0) (0.11 g, 0.095 mmol) was added and the mixture was refluxed for 4 hours.After confirming with HPLC and LC-MASS, the reaction was terminated. After removal of the solvent, it was extracted with MC / H2O. column (MC: Hex = 1: 4) and reprecipitated with MC / hexane to obtain a solid compound (1.24 g, yield = 81percent). | |
75.7% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water;Reflux; | To a round bottom flask was dissolved 20.0 g of dibenzofuran-4-boronic acid, 26 g of 4-bromo-1-iodo-benzene and 200 ml of 1,4-dioxane 40 ml of K2CO3 (2M) and 40 ml of Pd (PPh3) 4And the mixture was stirred under reflux. After confirming the reaction by TLC, water was added and the reaction was terminated. The organic layer was extracted with MC, filtered under reduced pressure and purified to obtain 23 g (yield: 75.7percent) of intermediate OP3 (4-(4-bromophenyl)dibenzo[b,d]furan)23g (yield: 75.7percent). |
56% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 70 - 80℃; for 3h; | Preparation of compound C-6-1 [133] After dissolving dibenzo[b,d]furan-4-yl boronic acid (20 g, 94.34 mmol), 1-bromo-4-iodo-benzene (53.4 ml, 188.68 mmol), Pd(PPh3)4 (5.45 g, 4.72 mmol) and K2CO3 (39.1 g, 283.01 mmol) in a mixture of toluene (900mL), EtOH (200mL) and distilled water (200mL), the reaction mixture was stirred for 3 hours at 70~80°C. After terminating the reaction, an aqueous layer was removed from the mixture by a gravity separation. And then, the obtained organic layer was concentrated and purified through column to obtain compound C-6-1 (17 g, 56 percent). |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 2 - 3h; | A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 ML) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine) palladium (0) (271 mg, 5 MOLpercent) in toluene (40 mL). 2N sodium carbonate (4.7 mL, 9.4 mmol) was added and the reaction was heated to 90°C (oil bath temp. ) for 2-3 hrs until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL). The combined extract was washed with water and brine. The ethereal solution was dried over anhydrous MGS04, filtered and concentrated in vacuo to yield 4- (4-BROMOPHENYL)-DIBENZOFURAN as a yellow solid, which was used immediately without further purification. A solution of 4-FORMYLPHENYLBORONIC acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-BROMOPHENYL)-DIBENZOFURAN (from the previous reaction) in toluene (40 mL). tetrakis- (Triphenylphosphine) palladium (0) (270 mg, 5 molpercent) and 2N sodium carbonate (4.7 mL, 9.4 mmol) were added and the reaction was heated to 100°C (oil bath temp. ) for 2-3 hrs until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL). The combined extract was washed with 0.5 N hydrochloric acid, water and brine and then dried over anhydrous MGS04, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 10-20percent ethyl acetate in hexane as eluent, afforded the title compound has a white solid (1.51g). | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 2 - 3h; | Example 7. 4' -Dibenzofuran-4-yl-biphenyl-4-carbaldehyde; EPO <DP n="91"/> A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 iriL) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine)palladium(O) (271 mg, 5 molpercent) in toluene (40 mL) . 2N sodium carbonate (4.7 mL, 9.4 mmol) was added and the reaction was heated to 900C (oil bath temp.) for 2-3 hrs until complete (TLC control) .The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL) . The combined extract was washed with water and brine. The ethereal solution was dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield 4- (4-bromophenyl) -dibenzofuran as a yellow solid, which was used immediately without further purification.A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-bromophenyl) -dibenzofuran (from the previous reaction) in toluene (40 mL) . tetrakis-(Triphenylphosphine)palladium(O) (270 mg, 5 molpercent) and 2N sodium carbonate (4.7 mL, 9.4 mmol) were added and the reaction was heated to 1000C (oil bath temp.) for 2-3 hrs until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL) . The combined extract was washed with 0.5 N hydrochloric acid, water and brine and EPO <DP n="92"/>then dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 10-20percent ethyl acetate in hexane as eluent, afforded the title compound has a white solid (1.5Ig) . | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 2 - 3h; | Example 1; 2-tert-Butoxycarbonylamino-3- (4 ' -dibenzofuran-4-yl-biphenyl-4- ylmethylsulfanyl) -propionic acid; Step 1; Preparation of 4' -Dibenzofuran-4~yl-biphenyl-4- carbaldehyde; A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 mL) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine) -palladium(0) (271 mg, 5 molpercent) in toluene (40 mL) . 2 N sodium carbonate (4.7 mL, 9.4 mmol) was added and then the reaction was heated to 90 0C (oil bath temp.) for 2-3 h until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL) . The combined organic extracts were washed with water and sat'd aq NaCl. The ethereal solution was dried over anhyd MgSC>4, filtered and concentrated in vacuo to yield 4- (4-bromophenyl) - dibenzofuran as a yellow solid, which was used immediately without further purification.A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-bromophenyl) -dibenzofuran (from the previous EPO <DP n="111"/>reaction) in toluene (40 mL) . Tetrakis- (Triphenylphosphine) - palladium(0) (270 mg, 5 molpercent) and 2 N sodium carbonate (4.7 mL, 9.4 mmol) were added and then the reaction was heated to 100 0C (oil bath temp.) for 2-3 h until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL) . The combined organic extracts were washed with 0.5 N hydrochloric acid, water and sat'd aq NaCl and then dried over anhyd MgSO4, filtered and concentrated in vacuo. Purification by flash column chromatography (10-20percent ethyl acetate in heptane) afforded the title compound has a white solid (1.5Ig) . | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 8h;Inert atmosphere; | Synthesis Example 10 (synthesis of Intermediate 10); Under an argon stream, 536 g of commercially-available 4-dibenzofuranboronic acid, 600 g of 4-iodobromobenzene, 41 g of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), 2.6 L of 2 M sodium carbonate (Na2CO3) solution, and 10 L of dimethoxyethane were charged, and the mixture was reacted at 80°C for 8 hours. The reactant was extracted with toluene and water, followed by drying with anhydrous sodium sulfate. The resultant was concentrated under reduced pressure, and the obtained crude product was subjected to column purification, whereby 257 g of white powder was obtained. By an FD-MS analysis, the white powder was identified as Intermediate 10. | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 10h;Inert atmosphere; Reflux; | Under an argon atmosphere, 300 mL of toluene and 150 mL of an aqueous solution of sodium carbonate having a concentration of 2 M were added to 28.3 g of 4-iodobromobenzene, 22.3 g of dibenzofuran-4-boronic acid, and 2.31 g of tetrakis (triphenylphosphine) palladium (0), and then the mixture was heated while being refluxed for 10 hours. Immediately after the completion of the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, 26.2 g of a white crystal were obtained. The crystal was identified as the Intermediate 21 by FD-MS analysis. | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 10h;Inert atmosphere; Reflux; | Under an argon atmosphere, 300 mL of toluene and 150 mL of a 2 mol/L aqueous solution of sodium carbonate were added to 28.3 g of 4-iodobromobenzene, 22.3 g of dibenzofuran-4-boronic acid, and 2.31 g of tetrakis(triphenylphosphine)palladium, and then the mixture was heated for 10 hours while being refluxed. Immediately after the completionof the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, 26.2 g of a white crystal were obtained. The white crystal was identified as the intermediate 3 by FD-MS analysis. | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; toluene; for 10h;Inert atmosphere; Reflux; | Under argon atmosphere, 150 ml of toluene, 150 ml of dimethoxyethane and 150 ml (300.0 mmol) of a 2M aqueous solution of Na2CO3 were added to 28.3 g (100.0 mmol) of 4-iodobromobenzene and 22.3 g (105.0 mmol) of dibenzofuran-4-boronic acid and 2.31 g (2.00 mmol) of Pd[PPh3]4. The resulting mixture was heated under reflux while stirring for 10 hours.After the reaction was completed, the sample was transferred to a separating funnel, followed by extraction with dichloromethane. The organic layer was dried with MgSO4, followed by filtration and concentration. The concentrated residue was purified by silica-gel column chromatography to obtain 26.2 g of white solids. The solids were identified as Intermediate 12 by FD-MS analysis. | |
28.5 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In toluene; at 80℃; for 8h;Inert atmosphere; | A three neck flask of 1000 ml was charged with 42.4 g of 4-dibenzofuranboronic acid, 56.0 g of 4-iodobromobenzene, 6.9 g of tetrakis-(triphenylphosphine)palladium (Pd(PPh3)4), 320 mL of a sodium carbonate (Na2CO3) solution of 2M and 320 mL of toluene under argon flow, and then they were reacted at 80° C. for 8 hours. The reaction solution was extracted with toluene/water, and the extract was dried on anhydrous sodium sulfate. This was concentrated under reduced pressure, and a crude product obtained was refined through a column, whereby 28.5 g of a white powder was obtained. |
27 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; for 12h;Inert atmosphere; | 20 g (94.4 mmol) of 4-dibenzofuranboronic acid, 28 g (99.2 mmol) of 1-bromo-4-iodobenzene, and 1.08 g (0.94 mmol) of tetrakistriphenylphosphine palladium were dissolved in 240 ml of toluene and 120 ml of ethanol under a nitrogen atmosphere in a flask, 120 ml of an aqueous solution in which 28 g (188.8 mmol) of potassium carbonate was dissolved was added thereto, and the mixture was agitated for 12 hours while being refluxed. When the reaction was complete, the resultant was extracted with ethyl acetate, the extracted solution was dried with magnesium sulfite and filtered, and the filtered solution was concentrated under a reduced pressure. The concentrated product was purified with n-hexane/dichloromethane (9:1 of a volume ratio) through silica gel column chromatography, obtaining 27 g of a white solid compound, an intermediate M-9 (89percent of a yield). |
5.92 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 24h; | In the 250 mE rounded-bottom flask, the compoundF 1(3.00 g, 14.15 mmol), the compoundA4 (4.00 g, 14.15mmol), tetrakis(triphenylphosphine)palladium(0) (0.82 g,0.71 mmol) and potassium carbonate (4.84 g, 35.00 mmol)were put into a mixture of toluene (70 mE), ethanol (35 mE)and water (17.5 mE) and stirred under the temperature of100° C. for 24 irs. Afier the completion of the reaction, the mixture was extracted and condensed using water and dichloromethane. The mixture was separated by a column using dichloromethane and n-hexane and precipitated using dichloromethane and petroleum ether. The precipitate was filtered such that the compound F2 was obtained. (5.92 g, 25.29 mmol) |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 24h; | To a 250 mL round bottom flask was added G1 (3.00 g, 14.15 mmol),G2 (4.00 g, 14.15 mmol), tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol) and potassium carbonate (4.84 g, 35.00 mmol) were dissolved in toluene (80 mL) Ethanol (20 mL) and water (20 mL) were added to the mixed solution,And the mixture was stirred at 100 DEG C for 24 hours. After completion of the reaction,Water and dichloromethane were used for extraction and concentration,The column was separated using dichloromethane and n-hexane.Then, the precipitate was prepared by using dichloromethane and petroleum ether, Filtration gave Compound G3 (3.95 g, 12.22 mmol). |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 24h; | Dibenzofuran-4-boronic acid (3.00 g, 14.15 mmol), 1-bromo-4-iodobenzene (4.00 g, 14.15 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol) in a 250 mL round- and potassium carbonate (4.84 g, 35.00 mmol) were added to a mixed solution of Toluene (80 mL), Ethanol (20 mL) and water (20 mL) and stirred at 100 ° C for 24 hours. After completion of the reaction, the reaction mixture was extracted with water and dichloromethane, concentrated, and then subjected to column separation using dichloromethane and n-hexane. Thereafter, a precipitate was prepared using dichloromethane and petroleum ether, and filtered to obtain Compound D1 (3.95 g, 12.22 mmol). |
3.95 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 24h; | Dibenzofuran-4-boronic acid (3.00 g, 14.15 mmol), 1-bromo-4-iodobenzene (4.00 g, 14.15 mmol), tetrakis (triphenylphosphine) palladium (0) (0.82 g, 0.71 mmol)Potassium carbonate (4.84 g, 35.00 mmol) was dissolved in toluene (80 mL)Was added to a mixed solution of ethanol (20 mL) and water (20 mL), and the mixture was stirred at 100 ° C for 24 hours. After completion of the reaction, the reaction mixture was extracted with water and dichloromethane,The mixture was concentrated, and the column was separated using dichloromethane and n-hexane.Then, the precipitate was prepared by using dichloromethane and petroleum ether,Filtration gave Compound G1 (3.95 g, 12.22 mmol). |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 2 - 3h; | A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 ML) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (TRIPHENYLPHOSPHINE)-PALLADIUM (O) (271 mg, 5 molpercent) in toluene (40 mL). 2 N sodium carbonate (4.7 mL, 9.4 mmol) was added and then the reaction was heated to 90 °C (oil bath temp. ) for 2-3 h until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL). The combined organic extracts were washed with water and sat'd aq NaCl. The ethereal solution was dried over anhyd MGS04, filtered and concentrated in vacuo to yield 4- (4-BROMOPHENYL)- dibenzofuran as a yellow solid, which was used immediately without further purification. A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 ML) was added to a stirred solution of the crude 4- (4-BROMOPHENYL)-DIBENZOFURAN (from the previous reaction) in toluene (40 mL). TETRAKIS- (TRIPHENYLPHOSPHINE)- palladium (0) (270 mg, 5 molpercent) and 2 N sodium carbonate (4.7 mL, 9.4 mmol) were added and then the reaction was heated to 100 °C (oil bath temp. ) for 2-3 h until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL). The combined organic extracts were washed with 0.5 N hydrochloric acid, water and sat'd aq NaCl and then dried over anhyd MGS04, filtered and concentrated in vacuo. Purification by flash column chromatography (10-20percent ethyl acetate in heptane) afforded the title compound has a white solid (1.51g). |
Yield | Reaction Conditions | Operation in experiment |
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With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 2 - 3h; | A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 ML) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine) palladium (0) (271 mg, 5 MOLpercent) in toluene (40 mL). 2N sodium carbonate (4.7 mL, 9.4 mmol) was added and the reaction was heated to 90°C (oil bath temp. ) for 2-3 hrs until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL). The combined extract was washed with water and brine. The ethereal solution was dried over anhydrous MGS04, filtered and concentrated in vacuo to yield 4- (4-BROMOPHENYL)-DIBENZOFURAN as a yellow solid, which was used immediately without further purification. A solution of 4-FORMYLPHENYLBORONIC acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-BROMOPHENYL)-DIBENZOFURAN (from the previous reaction) in toluene (40 mL). tetrakis- (Triphenylphosphine) palladium (0) (270 mg, 5 molpercent) and 2N sodium carbonate (4.7 mL, 9.4 mmol) were added and the reaction was heated to 100°C (oil bath temp. ) for 2-3 hrs until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL). The combined extract was washed with 0.5 N hydrochloric acid, water and brine and then dried over anhydrous MGS04, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 10-20percent ethyl acetate in hexane as eluent, afforded the title compound has a white solid (1.51g). | |
Example 7. 4' -Dibenzofuran-4-yl-biphenyl-4-carbaldehyde; EPO <DP n="91"/> A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 iriL) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine)palladium(O) (271 mg, 5 molpercent) in toluene (40 mL) . 2N sodium carbonate (4.7 mL, 9.4 mmol) was added and the reaction was heated to 900C (oil bath temp.) for 2-3 hrs until complete (TLC control) .The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL) . The combined extract was washed with water and brine. The ethereal solution was dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield 4- (4-bromophenyl) -dibenzofuran as a yellow solid, which was used immediately without further purification.A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-bromophenyl) -dibenzofuran (from the previous reaction) in toluene (40 mL) . tetrakis-(Triphenylphosphine)palladium(O) (270 mg, 5 molpercent) and 2N sodium carbonate (4.7 mL, 9.4 mmol) were added and the reaction was heated to 1000C (oil bath temp.) for 2-3 hrs until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL) . The combined extract was washed with 0.5 N hydrochloric acid, water and brine and EPO <DP n="92"/>then dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 10-20percent ethyl acetate in hexane as eluent, afforded the title compound has a white solid (1.5Ig) . | ||
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 100℃; for 2 - 3h; | Example 1; 2-tert-Butoxycarbonylamino-3- (4 ' -dibenzofuran-4-yl-biphenyl-4- ylmethylsulfanyl) -propionic acid; Step 1; Preparation of 4' -Dibenzofuran-4~yl-biphenyl-4- carbaldehyde; A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 mL) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (triphenylphosphine) -palladium(0) (271 mg, 5 molpercent) in toluene (40 mL) . 2 N sodium carbonate (4.7 mL, 9.4 mmol) was added and then the reaction was heated to 90 0C (oil bath temp.) for 2-3 h until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL) . The combined organic extracts were washed with water and sat'd aq NaCl. The ethereal solution was dried over anhyd MgSC>4, filtered and concentrated in vacuo to yield 4- (4-bromophenyl) - dibenzofuran as a yellow solid, which was used immediately without further purification.A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 mL) was added to a stirred solution of the crude 4- (4-bromophenyl) -dibenzofuran (from the previous EPO <DP n="111"/>reaction) in toluene (40 mL) . Tetrakis- (Triphenylphosphine) - palladium(0) (270 mg, 5 molpercent) and 2 N sodium carbonate (4.7 mL, 9.4 mmol) were added and then the reaction was heated to 100 0C (oil bath temp.) for 2-3 h until complete (TLC control) . The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL) . The combined organic extracts were washed with 0.5 N hydrochloric acid, water and sat'd aq NaCl and then dried over anhyd MgSO4, filtered and concentrated in vacuo. Purification by flash column chromatography (10-20percent ethyl acetate in heptane) afforded the title compound has a white solid (1.5Ig) . |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 2 - 3h; | A solution of dibenzofuran-4-boronic acid (1.0 g, 4.7 mmol) in ethanol (10 ML) was added to a stirred solution of 1- bromo-4-iodobenzene (1.33 g, 4.7 mmol) and tetrakis- (TRIPHENYLPHOSPHINE)-PALLADIUM (O) (271 mg, 5 molpercent) in toluene (40 mL). 2 N sodium carbonate (4.7 mL, 9.4 mmol) was added and then the reaction was heated to 90 °C (oil bath temp. ) for 2-3 h until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2 x 20 mL). The combined organic extracts were washed with water and sat'd aq NaCl. The ethereal solution was dried over anhyd MGS04, filtered and concentrated in vacuo to yield 4- (4-BROMOPHENYL)- dibenzofuran as a yellow solid, which was used immediately without further purification. A solution of 4-formylphenylboronic acid (0.9 g, 5.64 mmol) in ethanol (10 ML) was added to a stirred solution of the crude 4- (4-BROMOPHENYL)-DIBENZOFURAN (from the previous reaction) in toluene (40 mL). TETRAKIS- (TRIPHENYLPHOSPHINE)- palladium (0) (270 mg, 5 molpercent) and 2 N sodium carbonate (4.7 mL, 9.4 mmol) were added and then the reaction was heated to 100 °C (oil bath temp. ) for 2-3 h until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated, the aqueous phase being further extracted with ethyl acetate (2 x 20 mL). The combined organic extracts were washed with 0.5 N hydrochloric acid, water and sat'd aq NaCl and then dried over anhyd MGS04, filtered and concentrated in vacuo. Purification by flash column chromatography (10-20percent ethyl acetate in heptane) afforded the title compound has a white solid (1.51g). |
Yield | Reaction Conditions | Operation in experiment |
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With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 10h;Reflux; Inert atmosphere; | [Example-of-Synthesis 1] Synthesis of Compound 1 [Show Image] Under an argon atmosphere, 30 mL of dimethoxyethane (DME) and 15 mL of a 2-M aqueous solution of sodium carbonate were added to 3.22 g (10.0 mmol) of <strong>[955959-84-9]4-(4-bromophenyl)dibenzofuran</strong>, 3.83 g (11.0 mmol) of 10-(2-naphthyl)anthracene-9-boronic acid, and 0.231 g (0.200 mmol) of tetrakis(triphenylphosphine)palladium(0), and the mixture was refluxed under heat for 10 hours. After the completion of the reaction, the resultant was cooled to room temperature. The precipitated solid was taken by filtration, washed with methanol, water, and methanol in the stated order, and dried under reduced pressure. The resultant solid was recrystallized with toluene, whereby 4. 20 g of a pale yellow crystal were obtained. Mass spectral analysis confirmed the following: the crystal was the target product and had an m/e of 546, which was indicative of the molecular weight of the target product, i.e., 546.20. |
Yield | Reaction Conditions | Operation in experiment |
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With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; at 80℃; for 8h;Inert atmosphere; | Synthesis Embodiment 1 (synthesis of Compound H1); Under an argon stream, 2.5 g of Intermediate 6, 6.8 g of Intermediate 10, 2.6 g of sodium t-butoxide (manufactured by Hiroshima Wako Co., Ltd.), 92 mg of tris(dibenzylideneacetone)dipalladium(0) (manufactured by Aldrich Chemical Company, Inc.), 42 mg of tri-t-butylphosphine, and 100 mL of dehydrated toluene were charged, and the mixture was reacted at 80°C for 8 hours. After the reactant was cooled, 500 mL of water was added thereto, and the mixture was filtered with celite. The filtrate was extracted with toluene and dried with anhydrous magnesium sulfate. The resultant was concentrated under reduced pressure, and the obtained crude product was subjected to column purification. The purified product was recrystallized with toluene, followed by filtration and drying, whereby 5.1 g of pale yellow powder was obtained. By an FD-MS analysis, the pale yellow powder was identified as Compound H1. |
Yield | Reaction Conditions | Operation in experiment |
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With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; at 80℃; for 8h;Inert atmosphere; | [Example-of-Synthesis 1 (Synthesis of Compound H1) ]; Under an argon gas flow, 6.5 g of Intermediate 5, 9.5 g of Intermediate 12, 2.6 g of t-butoxy sodium (manufactured by Hiroshima Wako Co., Ltd.), 92 mg of tris (dibenzylideneacetone) dipalladium(0) (manufactured by SIGMA-ALDRICH Corn.), 42 mg of tri-tert-butylphosphine and 100 ml of dehydrated toluene were placed and the reaction was allowed to proceed at 80°C for 8 hours. The resultant solution was cooled down, added with 500 ml of water and filtered through sellite. The resultant filtrate was extracted with toluene, and the extract was dried over dehydrated magnesium sulfate. The dried substance was condensed under reduced pressure and the coarse product was subjected to column purification. The purified substance was re-crystallized with a use of toluene and after the resultant crystal was taken by filtration, the crystal was dried and as a result, 8.1 g of a pale yellow powder was obtained. The pale yellow powder was identified as Compound H1 from the result in accordance with the FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
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94% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene; at 65℃; for 4h;Inert atmosphere; | General procedure: 6 g of 1,3-dibromo-5-iodobenzene, 2.2 g of phenylboronic acid, 1.5 g of tetrakis(triphenylphosphine)palladium(0),4.6 g of potassium carbonate, 60 ml of toluene, and 20 ml of methanol were placed in a 250 ml round-bottomed three-necked flask under a nitrogen atmosphere and stirred at 65°C for 4 hours.The reaction solution was cooled and extracted with dichloromethane and water. The extracted solution was concentrated, and then the concentrated solution was subjected to column chromatography using a mixed solvent of dichloromethane and n-hexane and concentrated to thereby obtain 6.08 g of 3,5-dibromobiphenyl (yield: 71percent). |
Yield | Reaction Conditions | Operation in experiment |
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With potassium carbonate;copper; In decalin; at 190℃; for 96h;Inert atmosphere; | <Synthesis Example 1-15 (synthesis of Intermediate 1-15)> In a stream of argon, 185 g of 1-acetamide (manufactured by TOKYO CHEMICAL INDUSTRY CO., LTD.), 323 g of Intermediate 1-6 (manufactured by Wako Pure Chemical Industries, Ltd.), 544 g of potassium carbonate (manufactured by Wako Pure Chemical Industries, Ltd.), 12. 5 g of a copper powder (manufactured by Wako Pure Chemical Industries, Ltd.), and 2 L of decalin were loaded and subjected to a reaction at 190°C for 4 days. After the reaction, the resultant was cooled, and then 2 L of toluene were added to the resultant. The insoluble portion was taken by filtration. The product taken by filtration was dissolved in 4.5 L of chloroform, and then the insoluble portion was removed. After that, the remainder was subjected to an activated carbon treatment and concentrated. 3 liters of acetone were added to the resultant, and then 181 g of the precipitated crystal were taken by filtration. The crystal was identified as Intermediate 1-15 by FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
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With tri-tert-butyl phosphine; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 18h;Inert atmosphere; | In a stream of argon, 6.5 g of the intermediate-14', 8.8 g of the intermediate-20', 2.6 g of t-butoxy sodium, 92 mg of tris(dibenzylideneacetone)dipalladium, 42 mg of tri-t-butylphosphine, and 100 ml of dry toluene were loaded into a 300-ml three-necked flask, and then the mixture was subjected to a reaction at 80°C for 8 hours. After having been cooled, the reaction product was poured into 500 ml of water, and then the mixture was subjected to celite filtration. The filtrate was extracted with toluene, and was then dried with anhydrous magnesium sulfate. The dried product was concentrated under reduced pressure. The resultant coarse product was subjected to column purification, and was then recrystallized with toluene. The crystal was taken by filtration, and was then dried. As a result, 8.2 g of a pale yellow powder were obtained. The powder was identified as aromatic amine derivative (H-1') by FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
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In a stream of argon, 5.9 g of acetamide, 32.3 g of the intermediate 3 , 2.70 g of copper iodide, 40.8 g of potassium carbonate, 6.3 g of N'N-dimethylethylenediamine, and 300 mL of xylene were loaded, and then the mixture was subjected to a reaction at 175°C for 19 hours. Further, 38.5 g of the intermediate 1 were loaded into the resultant, and then the mixture was subjected to a reaction at 175°C for 19 hours. After the resultant had been cooled, water was added so that the resultant was filtrated. The residue was washed with acetone, methanol, and water three times each. Thus, 28.4 g of an acetamide body of the intermediate 13 were obtained. 28.4 g of the acetamide body of the intermediate 13, 26.3 g of potassium hydroxide, 25 mL of water, and 40 mL of xylene were loaded, and then the mixture was subjected to a reaction at 175°C for 5 hours. After the resultant had been cooled, water was added so that the resultant was filtrated. The residue was washed with acetone, methanol, and water three times each, and was then purified with a short column (developing solvent: toluene). The resultant solid was washed with n-hexane and dried under reduced pressure. Thus, 16.6 g of a white solidwere obtained. The white solidwas identified as the intermediate 13 by FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
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With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; at 80℃; for 8h;Inert atmosphere; | In a stream of argon, 5.6 g of the intermediate 13, 3.2 g of the intermediate 3, 1.3 g of t-butoxy sodium (manufactured by Hiroshima Wako Ltd.), 46 mg of tris(dibenzylideneacetone)dipalladium (manufactured by Sigma-Aldrich, Inc), 21 mg of tri-t-butylphosphine, and 50 mL of dry toluene were loaded, and then the mixture was subjected to a reaction at 80°C for 8 hours. After having been cooled, 500 mL of water were added, and then the mixture was subjected to celite filtration. The filtrate was extracted with toluene and dried with anhydrous magnesium sulfate. The dried product was concentrated under reduced pressure, and then the resultant coarse product was subjected to column purification. The purified product was recrystallized with toluene, and then the recrystallized product was taken by filtration. After that, the resultant was dried. Thus, 5.6 g of apaleyellowpowder were obtained. The pale yellow powder was identified as the aromatic amine derivative (H1) by FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
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96% | Preparation of compound C-6-2 [135] After dissolving compound C-6-1 (17 g, 52.6 mmol) in THF (400 ml), and adding 2.5 M n-BuLi in hexane (31.5 ml, 78.9 mmol) to the reaction mixture in -78°C, the reaction mixture was stirred for 1 hour. The reaction mixture was stirred for 12 hours with adding B(Oi-Pr) (24.1 ml, 105.2 mmol) slowly to the reaction mixture. After terminating the reaction, purified water 20 mL was dropped slowly to the reaction mixture. The reaction mixture was extracted with EA/NH4Cl aqueous solution. The obtained organic layer was concentrated, was triturated with MC/hexane, and then was filtered to obtain compound C-6-2 (14.5 g, 96 percent). |
Yield | Reaction Conditions | Operation in experiment |
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50% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene; for 8h;Inert atmosphere; Reflux; | In an argon atmosphere, 50 ml of dehydrated xylene was added to a mixture of 3.2 g (10.0 mmol) of intermediate 1-5, 3.3 g (10.0 mmol) of intermediate 2-1, 0.14 g (0.15 mmol) of Pd2(dba)3, 0.087 g (0.3 mmol) of P(tBu)3HBF4, and 1.9 g (20.0 mmol) of sodium t-butoxide. The resultant mixture was refluxed for 8 h under heating. [0179] After the reaction, the reaction solution was cooled to 50 °C and filtered through celite and silica gel. The filtrate was concentrated and the obtained concentrate was purified by silica gel column chromatography, to obtain a white solid. The crude product was recrystallized from toluene, to obtain 2.9 g of white crystal, which was identified as the following aromatic heterocyclic derivative (H1) by FD-MS analysis (yield: 50percent). |
Yield | Reaction Conditions | Operation in experiment |
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81% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In hexane; toluene; at 90℃; for 7.5h;Inert atmosphere; | In this example, a method for synthesizing N-(l, r-biphenyl-4-yl)-N-[4-(dibenzofuran-4-yl)phenyl]-9,9-dimethyl-9H-fluoren-2-ami ne (abbreviation: FrBBiF-II) represented by Structural Formula (100) will be described. [0238] [0239] First, 2.1 g (6.6 mmol) of <strong>[955959-84-9]4-(4-bromophenyl)dibenzofuran</strong>, 2.4 g (6.7 mmol) of N-(l,l '-biphenyl-4-yl)-9,9-dimethyl-9H-fluoren-2-amine, and 1.9 g (20 mmol) of sodium tert-butoxide were put in a 200-mL three-neck flask and the air in the flask was replaced with nitrogen. To this mixture, 33 mL of toluene, 0.30 mL of a 10 % hexane solution of tri(ter/-butyl)phosphine, and 48 mg (0.1 mmol) of bis(dibenzylideneacetone)palladium(0) were added, and stirring was performed at 90 C for 7.5 hours. After the stirring, suction filtration through Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135), Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531 - 16855), and alumina was carried out to give a filtrate. The filtrate was concentrated to give a solid. The solid was purified by silica gel column chromatography (the developing solvent was hexane and toluene in a ratio of 3:1) to give a solid. The solid was recrystallized from toluene and hexane, so that 3.2 g of an objective solid was obtained in a yield of 81 %. A reaction scheme of this reaction is shown below. [0240] [0241] Using a train sublimation method, 1.0 g of the obtained solid was purified by sublimation. In the purification by sublimation, the pressure was 2.6 Pa, the flow rate of argon gas was 5.0 mL/min, and the temperature of the heating was 289 C. After the purification by sublimation, 0.99 g of a solid which was the object of the synthesis was obtained at a collection rate of 95 %. [0242] Results of measurement of the obtained solid by nuclear magnetic resonance ( NMR) are shown below. NMR (CDCI3, 500 MHz): delta = 1.46 (s, 6H), 7.18 (dd, J = 8.5 Hz, 2.5 Hz, 1 H), 7.26-7.48 (m, 14H), 7.53-7.56 (m, 2H), 7.60-7.68 (m, 6H), 7.86-7.91 (m, 3H), 7.99 (d, J = 7.5 Hz, 1 H). [0243] Thermogravimetry-differential thermal analysis (TG-DTA) of the obtained FrBBiF-II was performed. The measurement was conducted by using a high vacuum differential type differential thermal balance (TG/DTA 2410SA, manufactured by Bruker AXS Kappa.Kappa.)· The measurement was carried out under a nitrogen stream (a flow rate of 200 mL/min) and a normal pressure at a temperature rising rate of 10 C/min. The relationship between weight and temperature (thermogravimetry) shows that the 5 % weight loss temperature is 393 C, which is indicative of high heat resistance. [0244] FIGS. 13A and 13B are NMR charts. Note that FIG. 13B shows an enlarged part of FIG. 13A in the range of 7.00 ppm to 8.25 ppm. The measurement results confirmed that N-(l, -biphenyl-4-yl)-N-[4-(dibenzofuran-4-yl)phenyl]-9,9-dimethyl-9H-fluoren-2-ami ne (abbreviation: FrBBiF-II), which was the target substance, was obtained. [0245] Physical Properties of FrBBiF-Il FIG. 14A shows an absorption spectrum and an emission spectrum of FrBBiF-II in a toluene solution of FrBBiF-II, and FIG. 14B shows an absorption spectrum and an emission spectrum of a thin film of FrBBiF-II. The spectra were measured with a UV-visible spectrophotometer (V550, produced by JASCO Corporation). The spectra of FrBBiF-II in the toluene solution of FrBBiF-II were measured with a toluene solution of FrBBiF-II put in a quartz cell. The spectra of the thin film were measured with a sample prepared by deposition of FrBBiF-II on a quartz substrate by evaporation. Note that in the case of the absorption spectrum of FrBBiF-II in the toluene solution of FrBBiF-II, the absorption spectrum obtained by subtraction of the absorption spectra of the quartz cell and toluene from the measured spectra is shown in the drawing and that in the case of the absorption spectrum of the thin film of FrBBiF-II, the absorption spectrum obtained by subtraction of the absorption spectrum of the quartz substrate from the measured spectra is shown in the drawing. [0246] As shown in FIG. 14A, in the case of FrBBiF-II in the toluene solution, an absorption peak was observed at approximately 360 nm, and an emission wavelength peak was observed at approximately 415 nm (excitation wavelength: 366 nm). As shown in FIG. 14B, in the case of the thin film of FrBBiF-II, absorption peaks were observed at approximately 368 nm, 294 nm, 266 nm, 247 nm, and 209 nm, and an emission wavelength peak was observed at approximately 428 nm (excitation wavelength: 376 nm). Thus, it was found that absorption and light emission of FrBBiF-II occur in extremely short wavelength regions. [0247] The ionization potential of FrBBiF-II in a thin film state was measured by photoelectron spectroscopy (the measuring instrument: AC-2, manufactured by Riken Keiki, Co., Ltd.) in the air. The obtained value of the ionization potential was converted into a negative value, so that the HOMO level of FrBBiF-II was determined to be -5.61 eV. From the da... |
81% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In hexane; toluene; for 7.5h;Inert atmosphere; | First, 2.1 g (6.6 mmol) of <strong>[955959-84-9]4-(4-bromophenyl)dibenzofuran</strong>, 2.4 g of N-(4-biphenyl)-9,9-dimethyl-9H-fluoren-2-amine (6.7 mmol)and 1.9 g (20.0 mmol) of sodium tert-butoxide were placed in a 200 mL three-necked flask, and the inside of the flask was purged with nitrogen. Subsequently, 33.0 mL of toluene, 0.3 mL of a 10% hexane solution of tri(tert-butyl)phosphine and 47.8 mg (0.1 mmol) of bis (dibenzylideneacetone)palladium (0) were added to this mixture, And stirred for 7.5 hours. After stirring, filtration was carried out by suction filtration through Florisil (Wako Pure Chemical Industries, catalog number: 540-00135), Celite (Wako Pure Chemical Industries, catalog number: 531-16855) and alumina to obtain a filtrate. The obtained filtrate was concentrated to obtain a solid. The obtained solid was purified by silica gel column chromatography (developing solvent: hexane: toluene = 3: 1) to obtain a solid. The obtained solid was recrystallized from toluene and hexane to obtain 3.2 g of the target solid in a yield of 81%. |
81% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In hexane; toluene; for 7.5h;Inert atmosphere; | First, 2.1 g (6.6 mmol) of 4- (4-bromophenyl) dibenzofuran, 2.4 g of N- (1,1'-biphenyl) -4-yl-9,9 dimethyl-9H-fluoren- (6.7 mmol) and sodium tert-butoxide 1.9 g (20.0 mmol) were placed in a 200 mL three-necked flask, and the inside of the flask was purged with nitrogen. Subsequently, 33.0 mL of toluene, 0.3 mL of a 10% hexane solution of tri (tert-butyl) phosphine and 47.8 mg (0.1 mmol) of bis (dibenzylideneacetone) palladium (0) were added to this mixture, And stirred for 7.5 hours. After stirring, filtration was carried out by suction filtration through Florisil (Wako Pure Chemical Industries, catalog number: 540-00135), Celite (Wako Pure Chemical Industries, catalog number: 531-16855), alumina and a filtrate was obtained. The obtained filtrate was concentrated to obtain a solid. The obtained solid was purified by silica gel column chromatography (developing solvent: hexane: toluene = 3: 1) to obtain a solid. The obtained solid was recrystallized from toluene and hexane to obtain 3.2 g of the target solid in a yield of 81%. The reaction scheme of this reaction is shown below. |
44% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene;Reflux; Inert atmosphere; | In a 500mL flask, <strong>[955959-84-9]4-(4'-bromophenyl)dibenzofuran</strong> (4.2g), N-(4-biphenylyl)(9,9-dimethylfluoren-2-yl) amine (5g), bis(dibenzylideneacetone)palladium (0) (0.24g), sodium tert-butoxide (2.65g), toluene (75ml), and tri(tert-butyl)phosphine (0.22g) were mixed and added together and refluxed under nitrogen atmosphere. The reaction was monitored by thin layer chromatography. Upon completion of the reaction, it was quenched with water (50mL) and extracted with ethyl acetate (70mL). The organic layer was extracted with water (3x50mL) and dried over anhydrous sodium sulfate. The ethyl acetate layer was collected through Celite and further purified by column chromatography. Following this, the ethyl acetate layer was evaporated to dryness under vacuum rotavap to get HPLC purity exceeding 99% and a yellow solid 3.45g compound 1-13 (44%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 6.5h;Reflux; Inert atmosphere; | Example 3<Synthesis of 2-[(dibenzofuran-2-yl)benzene-4-yl)-7,9,9-trimethyl-10-phenylacridan (Compound 80)>1-bromo-4-(dibenzofuran-2-yl)benzene (11.0 g), 4,4,5,5-tetramethyl-2-(10-phenyl-2,9,9-trimethylacridan-7-yl)-[1,3,2]dioxaborolane (17.3 g), tetrakis(triphenylphosphine)palladium (0.78 g), potassium carbonate (7.05 g), toluene (110 ml), ethanol (18 ml), and water (25 ml) were added to a reaction vessel in a nitrogen atmosphere, heated, and stirred for 6.5 hours under reflux. After the mixture was allowed to cool to room temperature, water and toluene were added to perform liquid separation in order to collect an organic layer. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (support: silica gel, eluent: toluene/ heptane=1/4) to obtain a white powder of 2-[(dibenzofuran-2-yl)benzene-4-yl)-7,9,9-trimethyl-10-phenylacridan (Compound 80; 13.2 g; yield 71percent).The structure of the product white powder was identified by NMR. The 1H-NMR measurement result is shown in FIG. 3. 1H-NMR (THF-d8) detected 31 hydrogen signals, as follows. delta (ppm) = 8.18 (1H), 8.02-7.94 (3H), 7.84 (1H), 7.75-7.72 (2H), 7.71-7.62 (4H), 7.54 (1H), 7.49-7.29 (7H), 6.74 (1H), 6.32 (1H), 6.15 (1H), 2.27 (3H), 1.78 (6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 145℃; | 475 mg (1.00 mmol) of Intermediate (B), 388 mg (1.20 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 91.6 mg(0.100 mmol) of Pd2(dba)3, 100 mL (50percent in toluene, 0.200 mmol) of tri-tert-butylphosphine (ttbp), and 192 mg (2.00mmol) of sodium tert-butoxide were added to 10 mL of xylene, and then, the mixture was heated at a temperature of145°C while stirring. When the reaction stopped, the reaction product was cooled to room temperature and then subjectedto silica gel to perform filtering under a reduced pressure, and the filtration solution was concentrated under a reducedpressure. The product was subjected to silica gel column chromatography (ethylacetate: n-hexane = 1: 4 volume tovolume). The product was refined by recrystallization using toluene/methanol to obtain 465 mg (yield of 65percent) of Compound1 as a target compound. LC-Mass (calculated: 715.26 g/mol, found: M+1 = 716 g/mol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 145℃; | 474 mg (1.00 mmol) of Intermediate (D), 388 mg (1.20 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 91.6 mg(0.100 mmol) of Pd2(dba)3, 100 mL (50percent in toluene, 0.200 mmol) of tri-tert-butylphosphine (ttbp), and 192 mg (2.00mmol) of sodium tert-butoxide were added to 10 mL of xylene, and then, the mixture was heated at a temperature of145 °C while stirring. When the reaction stopped, the reaction product was cooled to room temperature and then subjectedto silica gel to perform filtering under a reduced pressure, and the filtration solution was concentrated under a reducedpressure. The product was subjected to silica gel column chromatography (ethylacetate: n-hexane = 1: 4 volume tovolume). The product was refined by recrystallization using toluene/methanol to obtain 494 mg (yield of 69percent) of Compound2 as a target compound. LC-Mass (calculated: 716.26 g/mol, found: M+1 = 717 g/mol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 145℃; | 474 mg (1.00 mmol) of Intermediate (F), 388 mg (1.20 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 91.6 mg(0.100 mmol) of Pd2(dba)3, 100 mL (50percent in toluene, 0.200 mmol) of tri-tert-butylphosphine (ttbp), and 192 mg (2.00mmol) of sodium tert-butoxide were added to 10 mL of xylene, and then, the mixture was heated at a temperature of145°C while stirring. When the reaction stopped, the reaction product was cooled to room temperature and then subjectedto silica gel to perform filtering under a reduced pressure, and the filtration solution was concentrated under a reducedpressure. The product was subjected to silica gel column chromatography (ethylacetate: n-hexane = 1: 4 volume tovolume). The product was refined by recrystallization using toluene/methanol to obtain 537 mg (yield of 75percent) of Compound3 as a target compound. LC-Mass (calculated: 716.26 g/mol, found: M+1 = 717 g/mol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 145℃; | 475 mg (1.00 mmol) of Intermediate (H), 388 mg (1.20 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 91.6 mg(0.100 mmol) of Pd2(dba)3, 100 mL (50percent in toluene, 0.200 mmol) of tri-tert-butylphosphine (ttbp), and 192 mg (2.00mmol) of sodium tert-butoxide were added to 10 mL of xylene, and then, the mixture was heated at a temperature of145 °C while stirring. When the reaction stopped, the reaction product was cooled to room temperature and then subjectedto silica gel to perform filtering under a reduced pressure, and the filtration solution was concentrated under a reducedpressure. The product was subjected to silica gel column chromatography (ethylacetate: n-hexane = 1: 4 volume tovolume). The product was refined by recrystallization using toluene/methanol to obtain 508 mg (yield of 71 percent) of Compound4 as a target compound. LC-Mass (calculated: 715.26 g/mol, found: M+1 = 716 g/mol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene; for 8h;Inert atmosphere; Reflux; | SYNTHESIS EXAMPLE 1 (Production of aromatic amine derivative H1) [0135] Under an argon atmosphere, into a mixture of 3.2 g (10.0 mmol) of the intermediate 1-1, 5.8 g (10.0 mmol) of the intermediate 2-1, 0.14 g (0.15 mmol) of Pd2(dba)3, 0.087 g (0.3 mmol) of P(tBu)3HBF4, and 1.9 g (20.0 mmol) of t-butoxysodium, 50 ml of dry xylene was added, and the resultant mixture was refluxed for 8 h under heating. [0136] After the reaction, the reaction liquid was cooled to 50 °C and filtered through celite/silica gel. The filtrate was condensed and the obtained condensate was purified by silica gel column chromatography to obtain a white solid. The crude product was recrystallized from toluene to obtain 3.7 g of a white crystal, which was identified as the aromatic amine derivative H1 by FD-MS analysis (yield: 45percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 120℃; for 12h;Inert atmosphere; | Synthesis of Compound 11Under an argon atmosphere, 9.70 g of Compound B, 7.11 g of 4-(4-bromobiphenyl)dibenzofuran, 1.45 g of tris(dibenzylideneacetone)dipalladium(O) (Pd2(dba)3)), 510 mg of tri-tert-butyl phosphine ((t-Bu)3P), 5.77 g of sodium-tert-butoxide were added to a 50 mL xylene solvent in a 500 mL three-necked flask, followed by heating and stirring at 120° C. for 12 hours. After cooling the reactant in air, water was added, and an organic layer was separated. Then, the solvent was distilled off. The crude product thus obtained was separated by silica gel column chromatography (using a mixed solvent of dichloromethane and hexane), and recrystallized using a mixed solvent of toluene/hexane to obtain 11.6 g of Compound 11 as a white solid (yield 80percent). [0077] (Identification of Compound 11) [0078] The chemical shift values of Compound 11 measured by 1H-NMR were 8.86-8.89 (m, 211), 8.65-8.70 (m, 3H), 8.51 (d, 1H), 8.43 (q, 2H), 8.20-8.30 (m, 2H), 7.80-7.88 (m, 5H), 7.51-7.76 (m, 12H), 7.20-7.49 (m, 7H). In addition, the molecular weight of Compound 11 measured by FAB-MS was 727. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 24h;Reflux; | To a round bottom flask was added 4- (4-bromophenyl) dibenzofuran (1.23 g, 3.8 mmol), aminobiphenyl (0.71 g, 4.19 mmol)sodium tert-butoxide (0.512 g, 5.33 mmol),tris (dibenzylideneacetone) dipalladium (0) (0.07 g, 0.076 mmol) was dissolved in 50 ml of toluene. tri-tert-butylphosphine (0.03 g, 0.15 mmol) was added and the mixture was refluxed for 24 hours.After confirming with HPLC and LC-MASS, the reaction was terminated. After removal of the solvent, it was extracted with MC / H2O. column (EA: Hex = 1: 4) and reprecipitated with MC / hexane. Vacuum drying and sublimation purification were conducted to obtain a solid compound (1.25 g, yield = 80%). |
78% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 4h;Reflux; Inert atmosphere; | To a round bottom flask Intermediate M-1 10g (30.9mmol) was dissolved into a 4-aminobiphenyl 6.3g (37.08mmol),sodium tert-butoxide 5.35g (55.6mmol) was dissolved to 155ml of toluene.Here Pd (dba) 2 0.178g (0.31mmol) and tri-tert-butylphosphine was put 0.125g (0.62mmol) in turn and the mixture was stirred under reflux for 4 hours under a nitrogen atmosphere. After the reaction the organic layer was then extracted with ethyl dry distilled over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product n- hexane / dichloromethane (7: 3 by volume) to yield a column of silica gel 9.92g (78% yield) of Intermediate M-5 the objective compound was purified by chromatography as a white solid. |
51% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 4h; | p-Biphenylamine (p-Biphenylamine) (19 g, 1.3 eq), 4- (4-bromophenyl) -dibenzofuran (4- (4-bromophenyl) -Dibenzofuran) (28 g, 1 eq), Pd 2 (dba) 3 (2.4 g, 0.03 eq), t-BuONa (12.5 g, 1.5 eq), t-Bu 3P (1.05 g, 0.06 eq), Toluene 400 ml are placed in a single round bottom flask (1-neck-R.B.F.) and stirred. (4h) The solid was filtered (28g) (toluene hot filter) N- [4- (4-dibenzofuranyl) phenyl] - [1,1'-biphenyl] -4-amine (N- [4- (4-dibenzofuranyl) phenyl] - [1,1'-biphenyl] -4-amine. (18 g, step yield = 51percent) |
3.05 g | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 100℃; for 24h; | In the 250 mE rounded-bottom flask, the compound Al (1.80 g, 10.64 mmol), the compound F2 (3.78 g, 11.70 mmol), tris(dibenzylideneacetone) dipalladium(0) (0.15 g, 0.16 mmol), (±)-2,2?-bis(diphenylphosphino)-l , 1 ?-binaphthalene(I3INAP) (0.20 g, 0.32 mmol) and sodium tertbutoxide(l.43 g, 14.89 mmol) were dissolved in toluene (100 mE) and stirred in the bath of the temperature of 100 C. for 24 hrs. After the completion of the reaction, toluene was removed, and the resultant was extracted and distilled under the reduced pressure using dichioromethane and water. After the silica gel colunm, the solvent was distilled under the reduced pressure such that the compound F3 was obtained. (3.05 g, 7.41 mmol) |
3.05 g | With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 100℃; for 24h; | To a 250 mL round bottom flask was added D1 (1.80 g, 10.64 mmol),G3 (3.78 g, 11.70 mmol), Tris (dibenzylideneacetone) dipalladium (0) (0.15 g, 0.16 mmol),(BINAP) (0.20 g, 0.32 mmol) and sodium tert-butoxide (1.43 g, 14.89 mmol) were added to a solution of (±) -2,2'-Bis (diphenylphosphino) -1,1'- binaphthaleneAfter dissolving in toluene (100 mL)After stirring for 24 hours at 100 C in a bath, when the reaction is completeToluene was removed, and the residue was extracted with dichloromethane and water. The residue was subjected to vacuum distillation. The residue was subjected to silica gel column, and the solvent was distilled off under reduced pressure to obtain Compound G4 (3.05 g, 7.41 mmol). |
3.05 g | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 100℃; for 24h; | To a 250 mL round bottom flask was added 4-phenylaniline (1.80 g, 10.64 mmol), D1 (3.78 g, 11.70 mmol), Tris (dibenzylideneacetone) dipalladium (0) (0.15 g, -Bis (diphenylphosphino) -1,1'-binaphthalene (BINAP) (0.20 g, 0.32 mmol) and sodium tert-butoxide (1.43 g, 14.89 mmol) were dissolved in toluene (100 mL) After completion of the reaction, the reaction mixture was stirred for 24 hours. Toluene was removed, and the residue was extracted with dichloromethane and water. The residue was subjected to vacuum distillation. The silica gel column was distilled under reduced pressure to obtain Compound D2 (3.05 g, 7.41 mmol). |
3.05 g | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 100℃; for 24h; | To a 250 mL round bottom flask was added 4-aminobiphenyl (1.80 g, 10.64 mmol),G1 (3.78 g, 11.70 mmol), Tris (dibenzylideneacetone) dipalladium (0) (0.15 g, 0.16 mmol), (±) -2,2'-Bis (diphenylphosphino) -1,1'- binaphthalene (BINAP) g, 0.32 mmol) and sodium tert-butoxide (1.43 g, 14.89 mmol)After dissolving in toluene (100 mL)The reaction mixture was stirred at 100 C for 24 hours. After the reaction was completed, toluene was removed, and the residue was extracted with dichloromethane and water. The residue was subjected to vacuum distillation, After silica gel column, the solvent was distilled off under reduced pressure to obtain Compound G2 (3.05 g, 7.41 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tri-tert-butyl phosphine; palladium diacetate; potassium carbonate; In o-xylene; at 140℃; for 6h;Inert atmosphere; | In a stream of nitrogen, was added 2-chlorocarbazole 3.0g (14.9mmol) in 50mL three-necked flask, 1-bromo-4-(4-dibenzofuranyl)benzene, 4.8g (14.9mmol), potassium carbonate 4.1g (29.8mmol), o-xylene 25mL, palladium acetate, 67mg (0.29mmol) and tri (tert-butyl) phosphine 210mg (1.0mmol), stirred at 140 °C 6 hours. After cooling to room temperature, water was added 10mL, the organic layer was separated. The organic layer was washed with water, washed sequentially with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (mixed solvent of toluene and hexane (volume ratio = 1: 2)) was purified, isolated 2-chloro-9-(4-(4-dibenzofuran-yl)phenyl)carbazole as a white powder 5.4g (12.1mmol) (yield 81percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 3h;Inert atmosphere; | The compound 10.0 g (35.74 mmol), synthesized under the nitrogen air current in the preparation example 2 4 - (4-bromophenyl) dibenzo [b,d] furan of 11.55 g (35.74 mmol), the Pd 2 (dba) 3 of 0.98 g (1.07 mmol), P (t-bu) 3 of 0.72 g (3.57 mmol), and the NaO (t-bu) and toluene (200 ml) of 8.59 g (89.36 mmol) were mixed and it was stirred in 110 for 3hours. It extracted in the dichloromethane after the reaction termination and the MgSO 4 was put and it filtered. The intended compound 14.36 g (yield: 77 percent) was obtained using the column chromatography after the solvent of the filtered organic layer was removed |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; for 8h;Inert atmosphere; Reflux; | In the argon atmosphere, weighing intermediate respectively (1-1) 3.2g (10.0mmol), intermediate (A-2-1) 5.8g (10.0mmol), Pd2(dba)30.14g (0.15mmol), P (tBu)3HBF40.087g (0.3mmol), tertiary butyl alcohol sodium 1.9g (20.0mmol), adding anhydrous xylene 50 ml, heating reflux for 8 hours.After the reaction, the reaction mixture is cooled to 50 °C, filtered through diatomaceous earth/silica gel, concentrated filtrate. The obtained concentrated residue after being refined with silica gel column chromatography, using toluene recrystallization, get 2.9g of the white crystal (yield 35percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 60℃; for 12h;Inert atmosphere; | In a round bottom flask, 11.2 g (27.42 mmol) of intermediate K-10, 8.86 g (27.42 mmol) of intermediate M-1, 0.25 g (0.274 mmol) Pd2 (dba) 3, 0.133 g (0.274 mmol) of P(t-Bu)3 and 3.95 g (41.13 mmol) of NaO(t-Bu) suspended in 300 ml of toluene. And then stirred at 60 C for 12 hours. When the reaction was completed, distilled water was added thereto, and the mixture was stirred for 30 minutes and extracted, and the organic layer obtained therefrom was subjected to column chromatography using tannin (hexane/dichloromethane = 9:1 (vol/vol)). , obtained 19.5 grams of intermediate B-117 (yield 88%) |
73% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; for 15h;Inert atmosphere; Reflux; | 250 mL round bottom flask at the N-phenyl-3,3'-bi-carbazole 6.3 g (15.4 mmol), 4 - (4 - bromophenyl) dibenzo [b, d] furan 5.0g (15.4 mmol), sodium t-butoxide, 3.0 g (30.7 mmol), tris (dibenzylideneacetone) di palladium 0.9 g (1.5mmol) and 1.2 mL tree t- butylphosphine (50% in the mixture of toluene) and 100 mL of xylene for 15 hours under a nitrogen gas stream, andIt was not heated to reflux. The resulting mixture was filtered therefrom the crystallized solid was added to 300 mL of methanol, andAfter removal of benzene by dissolved in a cycle filtration with a silica gel / Celite, and an appropriate amount of an organic solvent, and recrystallized with methanol ofTo give a simplified A63 (7.3 g, 73% yield). |
73% | With tris-(dibenzylideneacetone)dipalladium(0); trineopentylphosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; for 15h;Inert atmosphere; Reflux; | 6.3 g (15.4 mmol) of N-phenyl-3,3-bicarbazole, 5.0 g (15.4 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 3.0 g (30.7 mmol) of sodium t-butoxide, 0.9 g (1.5 mmol) of tris(dibenzylideneacetone)dipalladium, and 1.2 mL of tri t-butylphosphine (50% in toluene) were mixed with 100 mL of xylene in a 250 mL round flask, and the mixture was heated and refluxed under a nitrogen flow for 15 hours. The obtained mixture was added to 300 mL of methanol, and a solid crystallized therein was filtered, dissolved in dichlorobenzene, filtered with silica gel/Celite, and then, recrystallized with methanol after removing an appropriate amount of the organic solvent to obtain Intermediate B-137 (7.3 g, yield of 73%). (0267) calcd. C48H30N2O: C, 88.59; H, 4.65; N, 4.30; O, 2.46; found: C, 88.56; H, 4.62; N, 4.20; O, 2.43. |
73% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; for 15h;Reflux; Inert atmosphere; | 6.3 g (15.4 mmol) of N-phenyl-3,3-bicarbazole, 5.0 g (15.4 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 3.0 g (30.7 mmol) of sodium t-butoxide, 0.9 g (1.5 mmol) of tris(dibenzylideneacetone)dipalladium, and 1.2 mL of tri t-butylphosphine (50% in toluene) were mixed with 100 mL of xylene in a 250 mL round flask, and the mixture was heated and refluxed under a nitrogen flow for 15 hours. The obtained mixture was added to 300 mL of methanol, and a solid crystallized therein was filtered, dissolved in dichlorobenzene, filtered with silica gel/Celite, and after removing an appropriate amount of an organic solvent, recrystallized with methanol to obtain Compound B-78 (7.3 g, a yield of 73%). (0183) calcd. C48H30N2O: C, 88.59; H, 4.65; N, 4.30; O, 2.46. found: C, 88.56; H, 4.62; N, 4.20; 0, 2.43. |
73% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; for 15h;Inert atmosphere; Reflux; | 250 mL round bottom flask at the N-phenyl-3,3-bi-carbazole 6.3 g (15.4 mmol), 4-(4-bromophenyl)dibenzo[b,d]furan 5.0 g (15.4 mmol), sodium t-butoxide, 3.0 g (30.7 mmol), tris(dibenzylideneacetone)dipalladium 0.9 g (1.5 mmol) and tri-t-butylphosphine 1.2 mL (50% in toluene) to 100 mL of xylene and mixed to a stream of nitrogen under was heated to reflux for 15 hours. After the mixture obtained therefrom was filtered and the crystallized solid was added to 300 mL of methanol, dimethyl dissolved in chlorobenzene and filtered through a silica gel / celite and removed, and then an appropriate amount of an organic solvent, and recrystallized with methanol to compound B-137 (7.3 g was obtained in a yield of 73%). |
60% | With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 100℃; for 8h;Inert atmosphere; | Under an argon atmosphere, the intermediate body 3H-1 (2.36 g, 7.3 mmol), an intermediate body 3H-2 (3.0 g, 7.3 mmol), CuI (1.4 g, 7.3 mmol), tripotassium phosphate (2.3 g, 11 mmol), anhydrous dioxane (30 mL), and cyclohexanediamine (0.84 g, 7.3 mmol) were loaded in the stated order into a three-necked flask, and were then stirred at 100 C. for 8 hours. Water was added to the reaction liquid to precipitate a solid, and then the solid was washed with hexane and then with methanol. Further, the resultant solid was purified by silica gel column chromatography. Thus, a compound 3H (2.9 g, 60% yield) was obtained. The result of FD-MS analysis confirmed that the compound had a ratio m/e of 650 with respect to its molecular weight, i.e., 650. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; ammonia; sodium t-butanolate; In toluene;Reflux; | In a round bottom flask, 4.9 g of aniline, 30 g of starting material X1, t-BuONa 14.5 g, Pd2(dba)3 2.2 g, and (t-Bu)3P 2.3 m were dissolved in 200 ml of toluene, stirred at reflux. The reaction was confirmed by thin layer chromatography (TLC), and after adding water, the reaction was terminated. Use methyl cellulose (MC) to extract organic layers and reduce themAfter pressure filtration, column purification and recrystallization were carried out to obtain 16.2 g (yield 81percent) of IA-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 4h;Inert atmosphere; Reflux; | Intermediate M-1 15g (46.4mmol) in a round bottom flask and 9,9-Dimethyl-9H-fluoren-2-ylamine 4.8g (23.2mmol),sodium-t- butoxide 6.7g (69.6mmol) ofIt was dissolved in toluene into a 185ml. Here Pd (dba) 2 0.53g (0.928mmol) and tri-tert-butylphosphine was placed to 0.38g (1.86mmol) in turn and the mixture was stirred under reflux for 4 hours under a nitrogen atmosphere. After completion of the reaction and then extracted with toluene the organic layer was dried and distilled over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product n- hexane / dichloromethane (8: 2 by volume) to give compound 8 as a purification by a silica gel column chromatography as a white solid 14.4g (90percent yield). |
85% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 4h;Inert atmosphere; Reflux; | 15 grams (46.4 millimoles) of intermediate M-1, 4.9 g (23.2 mmol) of 9,9-dimethyl-9H-indol-2-amine and 6.7 grams (69.6 millimoles) Sodium tert-butoxide (NaOt-Bu) was placed in a round bottom flask, And 160 ml of toluene was added thereto to dissolve it. Subsequently, 0.85 g (0.928 mmol) of Pd(dba)2 was sequentially added thereto. And 0.45 g (1.86 mmol) of tri-tert-butylphosphine (P(t-Bu)3), and the mixture was refluxed under a nitrogen atmosphere and stirred for 4 hours. When the reaction was completed, the resultant was extracted with toluene and distilled water, and the organic layer obtained therefrom was dried over magnesium sulfate and filtered, and the filtered solution was concentrated under reduced pressure. Subsequently, the product obtained therefrom was purified by hydrazine column chromatography using n-hexane/dichloromethane (8:2 by volume) to obtain 27.4 g of Compound I-61 (yield: 85percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 5,5-dimethyl-1,3-cyclohexadiene; for 48h;Inert atmosphere; Reflux; | 21 g (64.7 mmol) of intermediate M-1, 1.74 g (29.4 mmol) of acetamide and 17.3 g (117.0 mmol) of potassium carbonate were placed in a round bottom flask, and 130 ml was added thereto. Xylene is allowed to dissolve. Subsequently, 1.12 g (5.88 mmol) of copper (I) iodide and 1.04 g (11.8 mmol) of N,N-dimethylethylidene diamine were sequentially added thereto, and the mixture was refluxed under a nitrogen atmosphere. Stir for 48 hours. When the reaction was completed, the resultant was extracted with toluene and distilled water, and the organic layer obtained therefrom was dried over magnesium sulfate and filtered, and the filtered solution was concentrated under reduced pressure. Subsequently, the product obtained therefrom was purified by hydrazine column chromatography using n-hexane/ethyl acetate (5:5 by volume) to obtain 15 g of intermediate K-5 (yield 94percent). |
93% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 5,5-dimethyl-1,3-cyclohexadiene; for 48h;Inert atmosphere; Reflux; | Intermediate To a round bottom flask M-1 31.9g (98.7mmol), acetamide 2.6g (44.42mmol), into potassium carbonate 24.5g (177.66mmol) was dissolved in 200ml of xylene was added. Here insert of copper iodide (I) 1.69g (8.88mmol) and N, N- dimethylethylene diamine to 1.56g (17.77mmol) in turn and then the mixture was stirred under reflux for 48 hours under a nitrogen atmosphere. After the reaction extracted with distilled water and toluene and the organic layer was dried with magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product n- hexane / ethyl acetate (7: 3 by volume), purified by silica gel column chromatography to give the M-31 as 24.05g (93percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 12h;Inert atmosphere; Reflux; | Intermediate M-1 in a round bottom flask 10.0g (30.9mmol) and M-32 15.5g (30.9mmol),Sodi um-t- butoxide placed 4.46g (46.35mmol) was dissolved was added to 155ml of toluene. Here Pd2 (dba) 3 0.28g (0.31mmol) and tri-tert-butylphosphine was placed to 0.18g (0.93mmol) in turn and the mixture was stirred under reflux for 12 hours under a nitrogen atmosphere. After the reaction extracted with distilled water and toluene and the organic layer was dried with magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product n- hexane / dichloromethane (8: 2 by volume) to yield the silica gel column chromatography to give compound 9 as 20.71g (90percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13.7 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 80℃; for 5h; | At 80C, 4-dibenzofuranboronic acid (13.3g), 1,4-dibromobenzene (10g), tetrakis(triphenylphosphine)palladium (3.02g), toluene (158mL), ethanol (65mL), water (65mL), and potassium carbonate (21.69g) were stirred for 5 hours. The reaction was monitored by thin layer chromatography. Upon completion of the reaction, it was quenched with water (100mL) and extracted with ethyl acetate (100mL). The organic layer was extracted with water (3x30mL) and dried over anhydrous sodium sulfate. The ethyl acetate layer was collected through Celite and further purified by column chromatography. Following this, the ethyl acetate layer was evaporated to dryness under vacuum rotavap to yield 13.7g 4-(4'-bromophenyl)dibenzofuran. |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; toluene; at 80℃; for 24h;Inert atmosphere; | Under nitrogen environment, compound G was dissolved in tetrahydrofuran / toluene (5: 1) and then 0.9 equivalent of compound F was added. After 4.4 equivalent of Potassium carbonate was dissolved in DI water, 0.05 equivalent of Pd (0) was added. The reaction mixture was then refluxed at 80 C. for 24 hours and the reaction was terminated. After extraction with organic solvent, the organic solvent was removed. Compound H was obtained by reprecipitation after a column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5 g | In a 250mL flask, 4-(4'-bromophenyl)dibenzo[b,d]furan (10g) and tetrahydrofuran (90mL) were mixed and stirred under nitrogen atmosphere and cooled to -78°C. At -78°C, n-butyllithium (18.8ml, 2.5M in n-hexane) was added and stirred for 2 hours. After 2 hours, trimethyl borate (16g) was added and the reaction was equilibrated to room temperature overnight. The reaction was monitored by thin layer chromatography. Upon completion of the reaction, 2N hydrochloric acid solution (60mL) was added and stirred for 1 hour. It was quenched with water (50mL) and extracted with ethyl acetate (70mL). The organic layer was extracted with water (3x50mL) and dried over anhydrous sodium sulfate. Following this, the ethyl acetate layer was evaporated to dryness under vacuum rotavap to get 4-(dibenzofuran-4-yl)phenylboronic acid (5g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Inert atmosphere; | In a 500mL flask, <strong>[955959-84-9]4-(4'-bromophenyl)dibenzofuran</strong> (10g), bis(4-biphenylyl)amine (12.7g), bis(dibenzylideneacetone)palladium (0) (0.62g), sodium tert-butoxide (6.9g), xylene (150ml), and tri(tert-butyl)phosphine (0.58g) were mixed and added together and refluxed under nitrogen atmosphere. The reaction was monitored by thin layer chromatography. Upon completion of the reaction, it was quenched with water (50mL) and extracted with ethyl acetate (70mL). The organic layer was extracted with water (3x50mL) and dried over anhydrous sodium sulfate. The ethyl acetate layer was collected through Celite and further purified by column chromatography. Following this, the ethyl acetate layer was evaporated to dryness under vacuum rotavap. 100mL of methanol was further added to precipitate the residue. It was filtered and dried under vacuum to get HPLC purity exceeding 99percent and a pale yellow solid 7.67g compound 1-7 (44percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 7h;Inert atmosphere; Reflux; | Argon atmosphere, the compound (vii) in a 100mL three-necked flask 1.50g, Compound (xi) 0.87g, bis(dibenzylideneacetone)palladium (0) (Pd(dba)2) 0.11g, tri-t-butylphosphine ((t-Bu)3P) 0.15g, was added to sodium t-butoxide 0.54g, it was heated under reflux for 7 hours in 45mL of toluene solvent. After air-cooling, water was added The organic layer was separated, and the solvent was distilled off. The crude product thus obtained was purified by silica gel column chromatography (dichloro methane and using a mixed solvent of hexane), toluene, and subjected to recrystallization with hexane mixed solvent to give the compound A-41 as a white solid 1.86g (89percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 7h;Inert atmosphere; Reflux; | In an argon atmosphere, in a three-necked 100mL flask, compound (x) 0.8g, the compound (xi) 0.54g, bis(dibenzylideneacetone)palladium (0) (Pd(dba)2) 0.06g, tri-t-butylphosphine ((t-Bu)3P) 0.12g, was added to sodium t-butoxide 0.3g, was heated under reflux for 7 hours in 30mL of toluene solvent. After air-cooling, water was added The organic layer was separated, and the solvent was distilled off. The crude product thus obtained was purified by silica gel column chromatography (dichloro methane and using a mixed solvent of hexane) was subjected to recrystallization with toluene and hexane mixture solvent to give the compound A-35 as a white solid 0.95g (80percent yield) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.3% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 105℃; for 24h;Inert atmosphere; | In a 250 ml three-necked flask, 0.012 mol of the raw material 1-1, 0.010 mol of the raw material II-1, and 150 ml of toluene were added and stirred under a nitrogen atmosphere.Then add 5×10-5 mol Pd2(dba)3, 5×10-5 mol P(t-Bu)3, 0.03 mol sodium tert-butoxide, heated to 105 C, refluxed for 24 hours, sampling the plate, showing no bromine remaining, the reaction is complete; naturally cooled to room temperature, filtered, and the filtrate is rotary evaporated to no fraction, and passed through a neutral silica gel column to obtain the desired product intermediate B-1; HPLC purity 99.93%, yield 77.3%; |
72% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 4h;Reflux; Inert atmosphere; | In a round bottom flask, Intermediate M-1 10g (30.9mmol) andintermediate compound M-5 9.6g (37.08mmol),sodium t-butoxide 5.35g (55.6mmol) dissolved in 155 mL toluene was added. Pd(dba) 2 0.178g (0.31mmol) and tri-tert-butylphosphine0.125g (0.62mmol) were added in order and the mixture was stirred under refluxfor 4 hours under a nitrogen atmosphere. After completion of the reaction, thereaction mixture was extracted with toluene, the organic layer was dried anddistilled over magnesium sulfate, filtered and the filtrate was concentratedunder reduced pressure. The product was subjected to silica gel columnchromatography using n- hexane / dichloromethane (7: 3 by volume) to give thetarget intermediate M-7 11.2 g (72%yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10.1 g | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In toluene; at 80℃; for 8h;Inert atmosphere; | A flask was charged with 5.5 g of aniline, 16.2 g of the intermediate 3, 6.8 g of sodium t-butoxide (manufactured by Hiroshima Wako Co., Ltd.), 0.46 g of tris(dibenzylideneacetone)dipalladium (O) (manufactured by Aldrich Co., Ltd.) and 300 mL of dehydrated toluene under argon flow to carry out reaction at 80° C. for 8 hours.After cooling down, 500 ml of water was added thereto, and the mixture was filtered through celite. The filtrate was extracted with toluene, and the extract was dried on anhydrous magnesium sulfate. This was concentrated under reduced pressure, and a crude product obtained was refined through a column and recrystallized from toluene. It was separated by filtration and then dried, whereby 10.1 g of a pale yellow powder was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.1 g | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 80℃; for 8h;Inert atmosphere; | A flask was charged with 3.4 g of N,N?-diphenylbenzidine, 6.8 g of the intermediate 3, 2.6 g of sodium t-butoxide (manufactured by Hiroshima Wako Co., Ltd.), 92 mg of tris(dibenzylideneacetone)-dipalladium (O) (manufactured by Aldrich Co., Ltd.), 42 mg of tri-t-butylphosphine and 100 mL of dehydrated toluene under argon flow to carry out reaction at 80° C. for 8 hours.After cooling down, 500 mL of water was added thereto, and the mixture was filtered through celite. The filtrate was extracted with toluene, and the extract was dried on anhydrous magnesium sulfate. This was concentrated under reduced pressure, and a crude product obtained was refined through a column and recrystallized from toluene. It was separated by filtration and then dried, whereby 4.1 g of a pale yellow powder was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With bis[1,2-bis(diphenylphosphino)ferrocene]-palladium(0); potassium acetate; In N,N-dimethyl-formamide; at 150℃; for 13h;Inert atmosphere; | I-9 (140 g, 433 mmol) was dissolved in 1,400 mL of dimethylforamide (DMF) in a nitrogen atmosphere, To this was added bis (pinacolato) diboron (132 g, 520 mmol)And 1,1-bis (diphenylphosphine) ferrocene) dichloropalladium (II) (3.54 g, 4.33 mmol) Potassium acetate (106 g, 1.083 mmol) was added and the mixture was heated at 150 ° C for 13 hours to reflux.After completion of the reaction, water was added to the reaction solution, the mixture was filtered,And dried in a vacuum oven.The residue thus obtained was separated and purified by flash column chromatography to obtain Compound I-10 (97.8 g, 61percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | In a nitrogen-purged reaction vessel,6.0 g of 5,7-dihydro-furo [2,3-a: 5,4-a '] dicarbazole synthesized in Example 1,12.3 g of 4- (4-bromophenyl) dibenzofuran,5.0 g of tert-butoxysodium and60 ml of tolueneWas added and nitrogen gas was passed through the mixture for 1 hour.Then, in the reaction vessel,0.6 g of tris (dibenzylideneacetone) dipalladium (O) and0.8 g of a toluene solution containing 50percent (w / v) tri-tert-butylphosphineWas added. The mixture was then heated and stirred at 95 [deg.] C for 18 hours. The mixture was cooled to room temperature, water was added thereto, and the mixture was extracted with toluene to obtain an organic layer. The organic layer was dehydrated with anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude product.The crude product was purified by column chromatography (carrier: silica gel, eluent: toluene / n-hexane) to obtain 2.7 g of a white powder of 5,7-dihydro-5,7-bis {4- (dibenzofuran- Yl) phenyl} -furo [2,3-a: 5,4-a '] dicarbazole (Compound 5) (yield, 18percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With palladium diacetate; sodium t-butanolate; CyJohnPhos; In toluene;Reflux; Inert atmosphere; | A mixture of 3.6 g (4.3 mmol) N4,N4?-di(biphenyl-4-yl)-N4-(10,10-dimethyl-10H-indeno[2,1-b]triphenylen-12-yl)biphenyl-4,4?-diamine, 1.6 g (5.0 mmol) of 4-(4-bromophenyl)dibenzo[b,d]furan, 0.025 g (0.1 mmol) of palladium(II)acetate, 0.07 g (0.19 mmol) of 2-(dicyclohexylphosphino)biphenyl, 0.65 g (7 mmol) of sodium tert-butoxide and 50 ml of toluene was refluxed under nitrogen overnight. After finishing the reaction, then cooled to room temperature. The organic layer was extracted with dichloromethane and water, dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica gel (hexane-dichloromethane) to give product 2.8 g (yield 61percent) as a yellow solid. MS (m/z, FAB+):1072.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; | 10.4g (yield 82percent) of the Compound G-32 was synthesized according to KR 2011-0118542. HRMS (70 eV, EI+): mlz calcd for C60H40N2:804.3140, found: 804. Elemental Analysis: C, 90percent; H, 5percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium phosphate; copper(l) iodide; rac-diaminocyclohexane; In 1,4-dioxane; at 100℃; for 48h;Inert atmosphere; | Compound 1) d.) 500 mg (1.55 mmol) <strong>[955959-84-9]4-(4-bromophenyl)dibenzofuran</strong>, 760 mg (1 .70 mmol) 2-(9H-carbazol-3- yl)-6-phenyl-benzimidazolo[1 ,2-a]benzimidazole, 990 mg (4.64 mmol) potassium phosphate tribasic, 60 mg (0.31 mmol) copper iodide in 10 ml dioxane are stirred under nitrogen at 100°C. 1.24 g (36.1 mmol) cis, trans 1 ,2-diaminocyclohexane are added. The reaction mixture is stirred for 48 h. The reaction mixture is poured in methanol. The product is filtered off and is washed with water, methanol 10 percent tatraic acid. Column chromatography on silica gel with chloroform gives the product. Yield 690 mg (65 percent) MS (APCI(pos), m/z): 691 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium phosphate; copper(l) iodide; rac-diaminocyclohexane; In 1,4-dioxane; at 90 - 100℃; for 64h;Inert atmosphere; | Example 4 (0834) (0835) 500 mg (1.55 mmol) <strong>[955959-84-9]4-(4-bromophenyl)dibenzofuran</strong>, 760 mg (1.70 mmol) 2-(9H-carbazol-3-yl)- 5-phenyl-benzimidazolo[1,2-a]benzimidazole, 990 mg (4.64 mmol) potassium phosphate tribasic, 60 mg (0.31 mmol) copper iodide in 10 ml dioxane are stirred under nitrogen at 90 °C. 1.24 g (36.1 mmol) cis,trans 1,2-diaminocyclohexane are added. The reaction mixture is stirred for 16 h. The reaction temperature is increased to 100 °C. The reaction mixture is stirred for 48 h at 100 °C under nitrogen. The reaction mixture is poured in 40 ml methanol. The product is filtered of and is washed with water, methanol 10 percent tatraic acid. Column chromatography on silica gel with chloroform gives the product. Yield 780 mg (73 percent) 1H NMR (400 MHz, THF-d8): ^ = 8.67 (d, 1H), 8.43 (d, 1H), 8.31-8.36 (m, 3H), 8.20-8.23 (m,1H), 8.11-8.16 (m, 2H), 8.05-8.08 (m, 2H), 7.32-7.95 (m, 20 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene; for 8h;Inert atmosphere; Reflux; | Under argon atmosphere, 8 · 31g (10mmol) of Intermediate B-1, 6.46g (20mmol) 4- (4-bromophenyl) dibenzofuran, 0.28g (0.3mmol) of tris (dibenzylideneacetone yl) dipalladium, 0.174 g (0.6 mmol) of tri-tert-butylphosphine tetrafluoroborate and 3.8g (20mmol) sodium tert-butoxide into the three-necked flask, followed by addition of 50ml of dry xylene was heated under reflux for 8 hours The Cooled to 50 ° C, filtered through celite / silica gel, and the filtrate was concentrated under reduced pressure. The resulting residue was purified on a silica gel column and then recrystallized from toluene to give 6.48 g of solid, which was compound BS1 in a yield of 78percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With bis(tri-t-butylphosphine)palladium(0); sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 11h;Inert atmosphere; Reflux; | To a 500 ml round-bottomed flask under nitrogen was added compound F (7.92 g, 16.30 mmol), after the solution was completely dissolved in 280 ml of xylene, sodium tert-butoxide (1.87 g, 19.41 mol) was added thereto, bis(tri-tert-butylphosphine)palladium(0) (0.08 g, 0.16 mmol) was added and the mixture was heated and stirred for 11 hours. The temperature was lowered to room temperature, and the base was removed by filtration. The xylene was concentrated under reduced pressure and recrystallized from ethyl acetate (180 ml) to obtain Compound 6 (8.45 g, yield: 75percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 24h;Inert atmosphere; Reflux; | The specific synthetic route of the compound is now provided:250ml of four bottles, in the atmosphere of nitrogen,0.01 mol of 2- (4-bromophenyl) -dibenzofuran, 0.025 mol of acridine,0.03 mol sodium tert-butoxide, 1 x 10-4 mol Pd2 (dba) 3, 1 x 10-4 mol tri-tert-butylphosphine,150ml toluene, heated reflux 24 hours, sampling point plate, the reaction is complete, natural cooling, filtration,The filtrate was steamed and passed through a silica gel column to give the target product with 99.0percent purity and 69.00percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 60 - 130℃; for 6h;Inert atmosphere; | 0.21 g of palladium(II) acetate, xylene (20 mL), and 0.76 g of tri-tert-butylphosphine were added.Stirred at 60 °C for 30 minutes. The above solution was added to a flask heated to 60°C under nitrogen to give the above compound 4 (16,18-Dihydrobenzo[4,5]furo[3,2-a]benzofurano[2',3':6,7]indolo[3,2-h]carbazole 7.4 g), 4-(4-bromophenyl)dibenzo[b,d]furan (13.2 g) and sodium tert-butoxide 5.2 g (54 mmol) were added to the above solution together with xylene (180 mL). Then, it heated up at 130 °C , and it heat-stirred for 6 hours. After cooling to room temperature, 200 mL of water was added. After the organic layer was extracted with chloroform, the organic layer was dried over MgSO4 , the solvent was removed, and silica gel column chromatography was performed, whereby Compound A-10 (6.4 g, 41percent) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 60 - 130℃; for 6h;Inert atmosphere; | 0.21 g of palladium(II) acetate, xylene (20 mL), and 0.76 g of tri-tert-butylphosphine are added,Stirred at 60 °C for 30 minutes.The above solution was added to a flask heated to 60°C under nitrogen to give the above compound 2 (7,9-Dihydrobenzo[4,5]furo[2,3-g]benzofurano[2',3':4,5]indolo[2,3-b]carbazole 7.4g), 4-(4-Bromophenyl)dibenzo[b,d]furan (13.2 g) and sodium tert-butoxide 5.2 g (54 mmol) were added to the above solution together with xylene (180 mL). Then, it heated up at 130 °C, and it heat-stirred for 6 hours. After cooling to room temperature, 200 mL of water was added. After the organic layer was extracted with chloroform, the organic layer was dried over MgSO 4 , the solvent was removed, and silica gel column chromatography was performed to give Compound A-9 (7.4 g, 47percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 90℃; for 1.5h;Inert atmosphere; | In a dry 2L three-necked flask, 26.5 g (81 mmol, 1.1 eq.) of Intermediate-1 obtained in Reaction Formula 1 and 23.8 g (73.6 mmol, 1.0 eq.) of <strong>[955959-84-9]4-(4-bromophenyl)-dibenzofuran</strong> were added. Then add dried and degassed 1000 ml of toluene as a solvent. Pass nitrogen for 15 minutes. Then add 10.6 g (110.4 mmol, 1.5 eq.) sodium tert-butoxide, A toluene solution (m/v, 10percent) of 1.3 g (2percent mol) of catalyst Pd2(dba)3 and 6.0 ml (4percent mol) P(t-bu)3. The temperature was raised to 90°C and the reaction was carried out for 1.5 hours. After the reaction was completed, the mixture was cooled to room temperature, adsorbed on activated charcoal, suction filtered, and the solvent was removed by spin-drying. Recrystallization from toluene and ethanol gave 30.6 g of Intermediate 2 in 73percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 90℃; for 2h;Inert atmosphere; | In a dry 3 L three-necked flask was added 23.4 g (70.5 mmol, 1.1 eq.) of intermediate-6 and 20.7 g.(64.1 mmol, 1.0 eq.) <strong>[955959-84-9]4-(4-bromophenyl)-dibenzofuran</strong>, and then dry and degassed 900 ml of toluene was added as a solvent, and nitrogen was passed for 15 minutes. Further add 12.3 g (128.2 mmol, 2.0 eq.) of sodium t-butoxide, 1.2 g (2percent mol) of catalyst Pd2(dba)3 and 5.2 ml (4percent mol) of P(t-bu)3 in toluene solution (m /v, 10percent). The temperature was raised to 90 ° C and the reaction was carried out for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, adsorbed with activated carbon, suction filtered, and the solvent was evaporated, and then recrystallized from toluene and ethanol to give 28 g of Intermediate-7 in a yield of 76percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 115℃; for 3h;Inert atmosphere; | Synthesized in Example 1,7, 13, 13-tetramethyl-7,13-dihydro-5H-indeno [1,2-b] acridine,10.9 g of 4- (4-bromophenyl) dibenzofuran,3.6 g of sodium tert-butoxide,100 ml of xylene was added to a reaction vessel purged with nitrogen,Nitrogen gas was bubbled through for 1 hour.Tris (dibenzylideneacetone) dipalladium(0) and 1.5 g of a toluene solution of tri-tert-butylphosphine (50percent, w / v) were added and heated,And the mixture was stirred at 115 ° C. for 3 hours. After cooling to room temperature,After addition of 100 ml of water, the organic layer was collected by extraction with toluene. The organic layer was dehydrated with anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a crude product.The crude product was purified by column chromatography (carrier: silica gel, eluent: toluene / n-hexane)7, 7, 13, 13-tetramethyl-5- {4-(Dibenzofuran-4-yl) phenyl} -7,13-Dihydro-5H-indeno [1,2-b] acridine(Compound 19) white powder 13.9 g(Yield: 80percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 100℃; | 4(4-bromophenyl)dibenzo[b,d]furan (138 mmol) and 4(9-ethyl-9H-indazol-1-yl)aniline (125.5 mmol) were added to the reaction vessel in that order. After tris(dibenzylideneacetone)dipalladium (6.3 mmol), tri-tert-butylphosphine (12.5 mmol), sodium t-butoxide (376.4 mmol), and toluene 1320 mL, the reaction was carried out at 100 ° C; The organic matter was extracted with diethyl ether and water, and the organic layer was dried over magnesium sulfate. Intermediate 1, 94.13 mmol (75percent), mass spectrum: theoretical 528.24, calculated 528.20; |
Tags: 955959-84-9 synthesis path| 955959-84-9 SDS| 955959-84-9 COA| 955959-84-9 purity| 955959-84-9 application| 955959-84-9 NMR| 955959-84-9 COA| 955959-84-9 structure
[ 1516-96-7 ]
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1-Bromo-4-(phenylmethoxy)benzene
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P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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