Structure of 902518-11-0
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CAS No. : | 902518-11-0 |
Formula : | C18H12BrN |
M.W : | 322.20 |
SMILES Code : | BrC1=C(C=CC=C1)N1C2=CC=CC=C2C2=CC=CC=C12 |
MDL No. : | MFCD23135883 |
InChI Key : | KEWDVYIULXXMPP-UHFFFAOYSA-N |
Pubchem ID : | 59465012 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 19 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 88.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
4.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.83 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.06 |
Solubility | 0.000281 mg/ml ; 0.000000872 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.56 |
Solubility | 0.000889 mg/ml ; 0.00000276 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.48 |
Solubility | 0.0000107 mg/ml ; 0.0000000331 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.23 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.86 |
* 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 |
---|---|---|
85% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 12h;Inert atmosphere; Reflux; | 20 g (119.61 mmol) of carbazole, 67.68 g (239.22 mmol) of 2-bromoidobenzene, 11.40 g (59.81 mmol) of copper iodide, and 33.06 g (239.22 mmol) of potassium carbonate were dissolved in xylene in a nitrogen atmosphere, and the mixture was refluxed while stirring. After 12 hours, the mixture was cooled to room temperature, distilled water was added thereto, and the mixture was subjected to extraction using methyl chloride (MC), dried using magnesium sulfate, and distilled under reduced pressure. The resultant was separation-purified using column chromatography to obtain 32.64 g (101.67 mmol, 85% yield) of Intermediate 1-1. |
56% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 48h;Inert atmosphere; Reflux; | (1) In the reaction flask carbazole 3.0g, o-bromo-iodobenzene 10.15g, 2.39 g copper iodide, 4.95g of potassium carbonate and 40mL of dry xylene, the reaction was refluxed for 48 hours nitrogen, was added 50mL of water quench off the reaction, extracted with dichloromethane, the solvent was evaporated, purified by column chromatography, a white precipitate was finally obtained 9- (2-bromophenyl) -9H- carbazole 2.5g, 56% yield. |
47% | With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 48h; | Carbazole (1 eq) and o-bromoiodobenzene (3 eq) cuprous iodide (0.05 eq); 11 g potassium carbonate (4 eq) was added to a three-neck bottle.Add anhydrous N,N-dimethylformamide (DMF) and react at 140 C for 48 h.After the reaction was completed, the reaction system was poured into water to precipitate a large amount of solid, and the solid was dissolved in dichloromethane, and the mixture was applied to a white solid (47%); |
29% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 100℃; for 20h;Inert atmosphere; Reflux; | Sigma aldrich in nitrogen (http://www. Sigmaaldrich. Com /) carbazole yarn (50 g, 299. 0 mmol) of toluene 0. 5 L senses a rotation velocity of the disk to, herein 1-bromo-2-iodobenzene sigma aldrich yarn (101. 5 g, 358. 8 mmol), bis (dibenzylideneacetone) palladium (0) (5. 16 g, 8. 97 mmol), tris-tert butylphosphine (3. 02 g, 15. 0 mmol) and sodium tert-butoxide (34. 5 g, 358. 8 mmol) in 100 C sequentially and at the reflux by heating at a 20. Complete after reaction solution at a water doesn't have any error frames, then dichloromethane (DCM) extraction of water to the MgSO4 anhydride after triggers number, filter and was, concentrating it under reduced pressure. Thus-obtained residue number intermediate that is forward separated into flash column chromatography I-3 (27. 9 g, 29%) a obtained. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Heating / reflux; | Carbazole (1.672 g, 10 mmol), l-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K CO , 2.7646 g, 20 mmol), copper iodide (CuI, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO ), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the resulting white solid compound of Formula a (800 mg, yield 25%).[123] MS: [M+H]+ = 323. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Reflux; Inert atmosphere; | Preparation Example 1Preparation of Starting Material Represented by Formula aCarbazole (1.672 g, 10 mmol), 1-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K2CO3, 2.7646 g, 20 mmol), copper iodide (Cud, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO4), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the resulting white solid compound of Formula a (800 mg, yield 25%).MS: [M+H]+=323. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Reflux; Inert atmosphere; | Preparation Example 1Preparation of Starting Material Represented by Formula aCarbazole (1.672 g, 10 mmol), 1-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K2CO3.2.7646 g, 20 mmol), copper iodide (CuI, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO4), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the desired white solid compound (800 mg, yield 25%).MS: [M+H]+=323. |
25% | With copper(l) iodide; potassium carbonate; In N,N-dimethyl acetamide; at 130℃; for 48h;Inert atmosphere; | General procedure: A mixture of carbazole(1.67 g, 10 mmol), 2-bromoiodobenzene (4.2 g, 15 mmol), K2CO3 (2.76 g, 20 mmol), CuI (0.95 g, 5 mmol) and DMA (100 mL) in a 250 mL three-necked flask was heated at 130 C for 48 h under nitrogen. After cooling, it was poured into water (200 mL) and extracted with CH2Cl2, the combined organic phase was washed with water and dried over MgSO4. After workup, the crude product was isolated by column chromatography (PE) to afford white powder (1.5 g, 25 %); Rf = 0.26 (PE); M. p.: 110 - 112 C; 1H NMR (CDCl3, 500 MHz) delta: 8.17(d, J = 7.7 Hz, 2H), 7.88 (d, J = 8.0 Hz, 1H), 7.52 (m, 2H), 7.43 (m, 3H), 7.31 (t, J = 7.33 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H); 13C NMR (CDCl3, 125 MHz) delta: 140.84, 136.77, 134.23, 131.13, 130.14, 128.80, 125.92, 123.85, 123.25, 120.33, 119.98, 110.01. |
25.5% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; at 120℃; | Carbazole (7.39 g, 0.0442 mol), 1-bromo-2-iodobenzene (25 g, 0.0883 mol), CuI (0.421 g, 2.22 mmol), K2CO3 (12.12 g, 0.0883 mol) in a 500 mL 2-neck flask Mol) were dissolved in xylene and refluxed and stirred at 120 C. The mixture was cooled to room temperature, extracted with CH2Cl2, dried over MgSO4, and then the solvent was removed. Hexane solvent to obtain 3.63 g (25.5%) of a white solid. |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; | Under nitrogen atmosphere, a mixture of carbazole (1.7 g), 1-bromo-2-iodobenzene (1.5 ml), potassium carbonate (2.8 g), copper iodide (95 mg), and xylene (25 ml) was refluxed. After cooling to ordinary temperature, the reaction product was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then, the solvent was removed under reduced pressure. The residue was passed through a silica gel column by using a hexane solvent, and then, the solvent was removed under reduced pressure. The obtained residue was vacuum-dried to obtain the intermediate a as a white solid (800 mg, 25% yield). MS: [M+H]+=323 |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; | Under nitrogen atmosphere, a mixture of carbazole (1.7 g), 1-bromo-2-iodobenzene (1.5 ml), potassium carbonate (2.8 g), copper iodide (95 mg), and xylene (25 ml) was refluxed. After cooling to ordinary temperature, the reaction product was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then, the solvent was removed under reduced pressure. The residue was passed through a silica gel column by using a hexane solvent, and then, the solvent was removed under reduced pressure. The obtained residue was vacuum-dried to obtain the intermediate a as a white solid (800 mg, 25% yield). MS: [M+H]+=323 |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Inert atmosphere; | Carbazole (1.7 g),1-bromo-2-iodobenzene (1.5 ml),Potassium carbonate (2.8 g),Copper iodide (95 mg) and xylene (25 ml) were refluxed under an atmosphere of nitrogen.After cooling to normal temperature, the product was extracted with ethyl acetate.After drying the extract with anhydrous magnesium sulfate,The solvent was removed under reduced pressure.Passed through a silica gel column using a hexane solvent, the solvent was removed under reduced pressure,The obtained residue was dried under vacuum to obtain an intermediate a (800 mg, 25% yield) as a white solid. |
With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Inert atmosphere; | 1.672 g of carbazole, 1.6 mL of 1-bromo-2-iodobenzene, 2.7646 g potassium carbonate, 95 mg of copper iodide, and 25 mL of xylene were refluxed in a nitrogen atmosphere. The mixture was cooled to room temperature, extracted with ethyl acetate, and dried with anhydrous magnesium sulfate to remove moisture, and the solvent was removed under reduced pressure. Silica gel column separation using a hexane solvent was conducted, thus obtaining a compound from which the solvent was then removed under reduced pressure, followed by vacuum drying, yielding 9-(2-bromophenyl)-9H-carbazole as a desired white solid intermediate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.4% | The starting material represented by Formula a (6.96 g, 21.6 mmol) was dissolved in 300 ml of purified THF (tetrahydrofuran) and cooled to -780C, and n-BuLi (2.5 M in hexane, 8.64 ml, 21.6 mmol) was slowly dropped thereon. Stirring was conducted at the same temperature for 30 min, and 4,4'-dibromobenzophenone (6.12 g, 18.0 mmol) was added thereto. After stirring was conducted at the same temperature for 40 min, the temperature was raised to normal temperature and stirring was carried out for an additional 3 hours. The reaction was completed in an ammonium chloride (NH Cl) aqueous solution, and extraction was conducted with ethyl ether. Water was removed from an organic material layer using anhydrous magnesium sulfate (MgSO ), and an organic solvent was then removed therefrom. The produced solid was dispersed in ethanol, stirred for one day, filtered, and vacuum dried to produce 10.12 g of intermediate material (96.4percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.4% | Preparation Example 2Preparation of Starting Material Represented by Formula bThe starting material represented by Formula a (6.96 g, 21.6 mmol) was dissolved in 300 ml of purified THF (tetrahydrofuran) and cooled to -78° C., and n-BuLi (2.5 M in hexane, 8.64 ml, 21.6 mmol) was slowly dropped thereon. Stirring was conducted at the same temperature for 30 min, and 4,4'-dibromobenzophenone (6.12 g, 18.0 mmol) was added thereto. After stirring was conducted at the same temperature for 40 min, the temperature was raised to normal temperature and stirring was carried out for an additional 3 hours. The reaction was completed in an ammonium chloride (NH4Cl) aqueous solution, and extraction was conducted with ethyl ether. Water was removed from an organic material layer using anhydrous magnesium sulfate (MgSO4), and an organic solvent was then removed therefrom. The produced solid was dispersed in ethanol, stirred for one day, filtered, and vacuum dried to produce 10.12 g of intermediate material (96.4percent yield). The intermediate solid was dispersed in 10 ml of acetic acid, ten drops of concentrated sulfuric acid were added thereto, and reflux was conducted for 4 hours. The resulting solid was filtered, washed with ethanol, and vacuum dried to produce 9.49 g of compound of Formula b (yield 96.8percent).MS: [M+H]+=565. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.0 g of <strong>[902518-11-0]9-(2-bromophenyl)-9H-carbazole</strong> as the intermediate of preparation example 8 was dissolved in 10 mL of purified tetrahydrofuran, and the resulting solution was cooled to -78 degree C, and 1.613 mL of butyllithium was slowly added dropwise. The mixture was stirred at the same temperature for 30 min, and 1.05 g of 4-bromobenzophenone was added. The mixture was stirred at the same temperature for 40 minutes, and then further stirred at room temperature for an additional 3 hours. The reaction was terminated with aqueous ammonium chloride, and the reaction mixture was extracted with ethyl ether. The organic layer was dewatered using anhydrous magnesium sulfate, and the organic solvent was then removed. The resulting solid was then dispersed in ethanol, stirred for one day, filtered and vacuum dried, thus obtaining an intermediate material. The solid thus obtained was dispersed in 10 ml of acetic acid, and 10 drops of concentrated sulfuric acid were added, after which the mixture was refluxed for 4 hours. The resulting solid was filtered, washed with ethanol, and vacuum dried, yielding 8-(4-bromophenyl)-8-phenyl-8H-indolo-[3,2,1-de]acridine compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.96 g of <strong>[902518-11-0]9-(2-bromophenyl)-9H-carbazole</strong> as the intermediate Preparation example 8 was dissolved in 10 mL of purified tetrahydrofuran, and the resulting solution was cooled to -78 degree C, and 8.64 mL of butyllithium was slowly added dropwise. The mixture was stirred at the same temperature for 30 minutes, and 6.12 g of 4,4'-dibromobenzophenone was added. The mixture was stirred for 40 minutes at the same temperature, and then further stirred at room temperature for additional 3 hours. The reaction was terminated with aqueous ammonium chloride, and the reacrtion mixture was extracted with ethyl ether. The organic solvent was dewatered using anhydrous magnesium sulfate, and the organic solvent was then removed. The resulting solid was dispersed in ethanol, stirred for one day, filtered, and vacuum dried, thus obtaining an intermediate material. The solid thus obtained was dispersed in 10 mL of acetic acid, and 10 drops of concentrated sulfuric acid were added, after which the mixture was refluxed for 4 hours. The resulting solid was filtered, washed with ethanol, and vacuum dried, yielding 8,8 -bis (4-bromophenyl)-8H-indolo [3,2,1-de] acridine compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.3% | (Setting-Up and Reaction) To a 200 mL four-necked round-bottomed flask, a three-way stopcock, a Teflon-coated magnetic stirring bar, a 20 mL dropping funnel, and a thermometer were attached, and the inside was purged with nitrogen. To this flask, <strong>[902518-11-0]N-(2-bromophenyl)carbazole</strong> (7) (8.8 g, 27.3 mmol, 1.0 eq.) obtained in the first step and anhydrous tetrahydrofuran (hereinafter, abbreviated as THF) (54.6 mL) were sequentially added, and the obtained reactant solution was cooled to -70C by use of a dry ice/acetone bath. Subsequently, a n-butyllithium (hereinafter, abbreviated as n-BuLi)/n-hexane solution (1.60 mol/L, 17. 9 mL, 28. 6 mmol, 1.05 eq.) was placed in the dropping funnel, and added dropwise over 15 minutes, while the reactant solution was being stirred, and the inside temperature was being kept at -50C or below. Then, the dropping funnel was rinsed with anhydrous n-hexane (1 mL) . The obtained cream-colored suspension was stirred at -70C for 1 hour. Then, an anhydrous THF (14 mL) solution of chlorodicyclohexylphosphine (hereinafter, abbreviated as Cy2PCl) (7.0 g, 30.1 mmol, 1.1 eq.) was placed in the dropping funnel, and added dropwise over 15 minutes, while the suspension was being stirred, and the inside temperature was being kept at -50 C or below (the suspension was dissolved rapidly). After completion of the dropwise addition, the dry ice/acetone bath was taken out, and the temperature of the reaction solution was raised to room temperature over 30 minutes, followed by stirring for further 30 minutes. (Post Treatment and Purification) After the reaction solution had been concentrated under reduced pressure, toluene and an aqueous solution of sodium hydrogen carbonate (2.3 g, approximately 1 eq.) were added to the residue. The mixture was transferred to a separating funnel, shaken and allowed to stand, and the layers were separated (Aqueous Layer 1: pH=9). Then, the organic layer was further washed with water (Aqueous Layer 2: pH=7). The solvent was distilled off from the organic layer under reduced pressure, and toluene and silica gel (0.7 g) were added to the obtained light brown residue. The mixture was stirred at room temperature for 10 minutes and filtered by use of diatomaceous earth, and the residue was washed with toluene. The filtrate was concentrated, until crystals were precipitated. Then, methanol was added, and the obtained white suspension was filtered. The product obtained by the filtration was washed with methanol, and then dried under reduced pressure to give 10.6 g of title compound (2-1) as a colorless powder. Isolated Yield: 88.3%. 1H NMR (300 MHz, CDCl3): delta=8.12 (d, J=7.5 Hz, 2H), 7.76 (dt, J=1.5, 4.8 Hz, 1H), 7.57-7.47 (m, 2H), 7.38-7.28 (m, 3H), 7.23 (dt, J=0.9, 6.9 Hz, 2H), 7.02 (d, J=8.1 Hz, 2H), 1.85-1.38 (m, 12H), 1.22-0.90 (m, 10H). 31P NMR (121 MHz, CDCl3): delta=-14.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | (1) The carbazole 8.36g (0.05mol), o-dibromobenzene 17.69g (0.075mol), potassium carbonate 17.97g (0.13mol) placed in the reactor, stirred, purged with nitrogen for 30min,1.91 g of cuprous iodide and 1.46 g of L-lysine were added and heated to 163 ° C. for 38 h.No raw material was detected by TLC, and a large amount of water was added to terminate the reaction. The solid was precipitated by stirring and dried under suction filtration to give 13.37 g of 9- (2-bromophenyl) carbazole as solid, yield 83percent. | |
55% | With copper(I) oxide; potassium phosphate; N,N`-dimethylethylenediamine; In toluene; at 120℃; for 72h; | 9-Carbazole (6.52 g, 39 mmol), 1,2-dibromobenzene (8 mL,66.3 mmol), copper(I) oxide (1.116 g, 7.8 mmol), N,N'-dimethylethylenediamine (1.70 mL, 15.6 mmol) and anhydrous potassium phosphate (18.21 g, 85.8 mmol) were mixed in 50 mL of anhydrous toluene and heated at 120 °C for 3 days. The crude reaction mixture was extracted with dichloromethane and water. The organic layerwas dried with anhydrous MgSO4, filtered, and evaporated. The crude product was purified by column chromatography on silica gelusing 1:30 dichloromethane/hexane. The white powder wasformed. (6.95 g, Yield 55percent) 1H NMR (300 MHz, CDCl3): delta (ppm)8.14-8.17 (d, 2H), 7.85-7.88 (d, 1H), 7.47-7.57 (m, 2H), 7.37-7.45(m, 3H), 7.27-7.32 (m, 2H), 7.05-7.08 (d, 2H). |
55% | With copper; potassium carbonate; In dimethyl sulfoxide; at 20℃; for 20.5h;Inert atmosphere; Reflux; | A 500-mL, three-necked round bottom flask was charged with 9.7 g (0.058 mol) of the compound carbazole in a nitrogen atmosphere and diluted with 200 mL of dimethylsulfoxide. 15 g of 1,2-dibromobenzene, 3.7 g of copper powder and 12 g of potassium carbonate were added to the diluted solution, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was heated and refluxed for 20 hours. The reaction solution was cooled to room temperature and extracted with dichloromethane and distilled water. The extract was dried and concentrated under reduced pressure to obtain 10.3 g (yield: 55percent) of Compound 11-1. |
53% | With copper(l) iodide; 18-crown-6 ether; In 1,2-dichloro-benzene; at 100 - 210℃;Inert atmosphere; Darkness; | Carbazole (1.6700 g, 10.0 mmol), o-dibromobenzene (2.40 mL, 20.0 mmol),Copper iodide (0.1900 g, 1.0 mmol), 18-crown-6 (0.1320 g, 0.5 mmol), 60mL o-dichlorobenzene was added to the reaction flask in turn, under nitrogen protection and dark conditions,Stir heated to 100-210°C, react for 5-100 hours, stop the reaction and slowly reduce to room temperature, Most of the solvent was distilled off under reduced pressure. The solid residue was suction filtered and washed with dichloromethane solution. The organic phase was combined. Concentration and column chromatography gave N-(2-bromophenyl)carbazole; (yield: 53percent) |
39% | With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In o-xylene; for 8h;Reflux; Inert atmosphere; | In a one-neck flask, carbazole (3.3g, 19.9mmol), o-dibromobenzene (4.5g, 19.9mmol), CuI (0.8g, 4.0mmol), 1,10-phenanthroline monohydrate (0.8g, 4.0mmol) and KOH (2.3g, 40mmol)were dissolved in o-x1ylene (50mL). The mixture was heated to reflux for 8h under nitrogen. After the reaction had all reacted, the mixture was allowed to cool to room temperature and then CH2Cl2 (50mL) was poured into the mixture. The organic layer was dried over anhydrous MgSO4 and concentrated this by a rotary evaporator. The crude materials were purified by silica gel column chromatography (petroleum ether/CH2Cl2=4: 1 v/v) to obtain a white solid 1.5g, 39percent. 1H NMR (400MHz, DMSO-d6, TMS) delta: 8.25 (d, J=7.6Hz, 2H), 8.00 (dd, J=8.0, 1.2Hz, 1H), 7.68 (m, 2H), 7.62?7.56 (m, 1H), 7.45?7.38 (m, 2H), 7.32?7.25 (m, 2H), 7.00 (d, J=8.0H, 2H). 13C NMR (126MHz, CDCl3) delta: 140.84, 140.49, 134.25, 131.16, 130.64, 130.17, 129.78, 128.83, 125.94, 123.24, 120.36, 119.99, 110.14, 110.03. HRMS (m/z): [M+H]? calcd for C18H12BrN, 322.0231; found, 322.0250. |
With copper(l) iodide; potassium carbonate; In N,N-dimethyl acetamide; for 24h;Inert atmosphere; Reflux; | A mixture of 9H-carbazole (5.5 g, 32.89 mmol), 1,2-dibromobenzene (11.64 g, 49.34 mmol), cupper iodide (3.13 g,16.45 mmol), and potassium carbonate (9.09 g, 65.79 mmol) inanhydrous N,N-dimethylacetamide (120 mL) was degassed withnitrogen for 30 min while stirring. The reaction mixture was thenrefluxed under a nitrogen atmosphere for 24 h. The crude mixturewas filtered, and the residue was washed thrice with dichloromethane(50 mL). The combined filtrates were evaporated to dryness.The residue was purified through column chromatography(silica gel, 50percent n-hexane in dichloromethane) to yield 9-(2-bromophenyl)-9H-carbazole as a white solid.1H NMR (500 MHz, CDCl3): d 7.06 (d, 2H, J 12 Hz), 7.28 (t, 2H,J 18 Hz), 7.39 (t, 3H, J 18 Hz), 7.43e7.52 (m, 2H), 7.84 (d, 1H,J 12 Hz), 8.14 (d, 2H, J 12 Hz). | |
With copper(l) iodide; potassium carbonate; In N,N-dimethyl acetamide; for 24h;Inert atmosphere; Reflux; | A mixture of 9H-carbazole (5.5 g, 32.89 mmol), 1,2-dibromobenzene (11.64 g, 49.34 mmol), copper iodide (3.13 g,16.45 mmol), and potassium carbonate (9.09 g, 65.79 mmol) inanhydrous N,N-dimethylacetamide (120 mL) was degassed withnitrogen for 30 min while stirring. The reaction mixture was thenrefluxed in nitrogen for 24 h. The crude mixture was filtered, andthe residue was washed with dichloromethane (3 x 50 mL). Thecombined filtrates were evaporated until they were dry The residue was purified by column chromatography (silica gel, 50percent n-hexanein dichloromethane) to give 9-(2-bromophenyl)-9H-carbazole as awhite solid.1H NMR (500 MHz, CDCl3): delta 7.06 (d, 2H, J = 12 Hz), 7.28 (t, 2H,J = 18 Hz), 7.39 (t, 3H, J = 18 Hz), 7.43-7.52 (m, 2H), 7.84 (d, 1H,J = 12 Hz), 8.14 (d, 2H, J = 12 Hz). 13C NMR (CDCl3): delta 110.0, 120.0,120.3, 123.2, 123.8, 125.9, 128.8, 130.1, 131.1, 134.2, 136.7, 140.8. |
Yield | Reaction Conditions | Operation in experiment |
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95% | With palladium diacetate; tricyclohexylphosphine; In N,N-dimethyl acetamide;Reflux; | Compound E (9 g, 28 mmol),Pd (OAc) 2 (1.9 g, 0.84 mmol),PCy3 (0.47 g, 1.68 mmol) was added to 100 mL of DMAc and the mixture was refluxed and stirred. After completion of the reaction, water was added, and the mixture was extracted with toluene (25 mL * 3 times)The obtained organic layer was dried over MgSO4, distilled under reduced pressure, and purified through short silica column chromatography (EtOAc: Hexane) to obtain compound J (6.5 g, 95%). |
89.5% | With N-benzyl-N,N,N-triethylammonium chloride; palladium diacetate; potassium carbonate; triphenylphosphine; In N,N-dimethyl-formamide; at 150℃; for 3h;Inert atmosphere; | The preparation method of the compound of formula M2 is as follows:2.87 g (8.0 mmol) of M1, 0.2 g (0.8 mmol) of benzyltriethylammonium chloride, and 5.5 g (40.0 mmol) of potassium carbonate were sequentially added to a 250 mL two-necked flask.Triphenylphosphine, 0.26 g (1.2 mmol) palladium acetate,100 mL of N,N-dimethylformamide,The reaction system is degassed and then protected with nitrogen.The mixture was heated to 150 C with stirring for 3 hours. After the reaction is completed, the system is cooled to room temperature and poured into water.Filter under reduced pressure and wash the filter residue with plenty of water.The filter residue was used in dichloromethane: petroleum ether = 1:20The (volume ratio) eluent was separated and purified on a silica gel column to obtain 1.7 g of M2 in a yield of 89.5%. |
83% | With Et3NBnCl; palladium diacetate; potassium carbonate; triphenylphosphine; In N,N-dimethyl acetamide; for 6h;Inert atmosphere; Reflux; | General procedure: A mixture of 3aa (200 mg, 0.62 mmol), anhydrous K2CO3 (428 mg, 3.1 mmol), PPh3 (60 mg, 0.22 mmol), BnEt3NCl (133 mg, 0.62 mmol) and Pd(OAc)2 (21 mg, 0.09 mmol) in DMA (50 mL) in a 100 mL three-necked flask was refluxed for 6 h under nitrogen, then it was cooled to room temperature and poured into ice-water (200 mL). Subsequent extraction with CH2Cl2 was made and the combined organic phase was washed with water and dried over MgSO4. After workup, the crude product was purified with PE (Rf = 0.41) to afford 4aa as a white solid (124.0 mg, 83 %); m. p.: 126 - 128 C; 1H NMR (CDCl3, 500 MHz) delta: 8.12 (d, J = 7.70 Hz, 2H), 8.02 (d, J = 7.4 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.55 (m, 3H), 7.34 (t, J = 7.53 Hz, 2H); 13C NMR (CDCl3, 125 MHz) delta: 143.75, 138.70, 130.03, 126.68, 123.14, 122.81, 121.67, 119.38, 118.45, 112.14; MS (EI): m/z=241[M+]. |
47% | With palladium diacetate; potassium carbonate; ammonium bromide; triphenylphosphine; In N,N-dimethyl acetamide; at 150℃; for 20h; | To a 3000-mL four-necked round-bottomed flask was added 22 g (0.069 mol) of the compound 11-1 prepared in Example 1-1, 1.6 g of palladium acetate (II), 3.6 g of triphenylphosphine, 43 g of potassium carbonate, 11 g of ammonium bromide and 2200 mL of dimethyl acetamide. The reaction solution was stirred at 150 C for 20 hours, and then dimethylacetamide was concentrated under reduced pressure. The concentrate was diluted with dichloromethane and extracted with dichloromethane and distilled water. The extract was dried and concentrated under reduced pressure. The obtained crude product was subjected to column separation to obtain 7.8 g (yield 47%) of Compound 11-2. |
Yield | Reaction Conditions | Operation in experiment |
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64% | 9-(2-Bromophenyl)-9H-carbazole (3.23g, 10.0mmol) was dissolved in anhydrous tetrahydrofuran (35mL) under nitrogen at -78C and n-butyllithium (2.5M in hexane, 4.0mL) was added dropwise slowly. The solution was stirred for 2h at -78C, followed by addition of a solution of (8-iododibenzo[b,d]furan-2-yl)(phenyl)methanone (3.2g, 8.0mmol) in anhydrous tetrahydrofuran (50mL) under nitrogen. The mixture was gradually warmed to room temperature and quenched with distilled water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4 and concentrated. The crude powdery product was placed in another two-neck flask (250mL) and dissolved in acetic acid (160mL). A catalytic amount of sulfuric acid (10mL) was then added and the solution was refluxed for 12h. After cooling to room temperature, white powder was filtered off and was purified by column chromatography using dichloromethane/n-hexane as an eluent. Final product was obtained as a white powder (3.2g, yield 64%). (0011) 1H NMR (400MHz, DMSO): delta 7.03 (d, 2H, J=3.5Hz), 7.09 (t, 3H, J=7.5Hz), 7.20 (t, 1H, J=7.5Hz), 7.26 (t, 1H, J=7.5Hz), 7.31 (t, 1H, J=7.5Hz), 7.41 (t, 2H, J=8.0Hz), 7.50 (d, 1H, J=4.0Hz), 7.55 (d, 1H, J=4.0Hz), 7.59-7.64 (m, 2H), 7.79 (d, 1H, J=5.0Hz), 7.92 (s, 1H), 8.13 (d, 1H, J=3.5Hz), 8.27 (d, 1H, J=4.0Hz), 8.32 (t, 2H, J=8.5Hz), 8.45 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
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80.2% | 9-(2-Bromophenyl)-9H-carbazole (1.93 g, 6 mmol) was dissolved in 80 mL THF in a 200 mL Schlenk tube under argon. After the solution was cooled to -78 C, n-butyl lithium (2.63 mL, 6.3 mmol) was added dropwise. The resulting mixture was allowed to stir for 1 h at -78 C, and then 3-bromofluorenone (1.56 g, 6 mmol) in 50 mL THF was added. After 1 h reaction at -78 C, the mixture was gradually warmed up to room temperature overnight. 5 mL water was added to the mixture and THF was evaporated under reduced pressure. The resulting solid was dissolved in 80 mL dichloromethane and washed with water (3 * 50 mL). Then the organic layer was separated, dried over Na2SO4, filtered and evaporated. The resulting solid was further purified by column chromatography using petroleum ether/dichloromethane (3.5/1, v/v) as eluent to afford 9-(2-(9H-carbazol-9-yl)phenyl)-3-bromo-9H-fluoren-9-ol (2.41 g, 80.2%). A mixture of 9-(2-(9H-carbazol-9-yl)phenyl)-3-bromo-9H-fluoren-9-ol (1.80g, 3.58mmol), acetic acid (40mL) and hydrochloric acid (4.5mL) was stirred at 65C for 14h. After cooling to room temperature, filtered and washed with ethanol. The resulting solid was further purified by column chromatography using petroleum ether/ dichloromethane (3/1, v/v) as eluent to afford a white powder (1.63g, 93.6%). |
Yield | Reaction Conditions | Operation in experiment |
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52% | 10169] <strong>[902518-11-0]9-(2-bromophenyl)-carbazole</strong> (20.9 g, 62.1 mmol) was dissolved in anhydrous tetrahydroffiran (THF) (200 ml) and then cooled to ?78° C. 2.5M n-butyllithium (n-Eu-Li) (24.8 ml, 62.1 mmol) was added for 30 minutes and then agitated at ?78° C. for 2 hours. Afier Structural Formula B (18.9 g, 56.4 mmol) was added at ?78° C., the temperature was increased to normal temperature, and the reaction was quenched by the ammonium chloride aqueous solution (aq. NH4C1). Afier the organic layer was separated, concentration was performed and purification was performed by the chromatography to obtain Structural Formula B-i (17.3 g, yield 52percent). |
Yield | Reaction Conditions | Operation in experiment |
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41% | <strong>[902518-11-0]9-(2-bromophenyl)-carbazole</strong> (iO g, 3i.0 mmol) was dissolved in anhydrous tetrahydroffiran (THF) (200 ml)and then cooled to ?78° C. 2.5M n-butyllithium (n-Eu-Li) (i2.4 ml, 3i.0 mmol) was added for 30 minutes and then agitated at ?78° C. for 2 hours. Afier Structural Formula C (7.3 g, 28.2 mmol) was added at ?78°C., the temperature was increased to normal temperature, and the reaction was quenched by the ammonium chloride aqueous solution (aq. NH4C1). Afier the organic layer was separated, concentration was performed and purification was performed by the chromatography to obtain Structural Formula C-i (5.8 g, yield 4ipercent). |
Yield | Reaction Conditions | Operation in experiment |
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43% | <strong>[902518-11-0]9-(2-bromophenyl)-carbazole</strong> (10 g, 31.0 mmol) was dissolved in anhydrous tetrahydroffiran (THF) (200 ml) and then cooled to ?78° C. 2.5M n-butyllithium (n-Eu-Li) (12.4 ml, 31.0 mmol) was added for 30 minutes and then agitated at ?78° C. for 2 hours. Afier Structural Formula D (7.3 g, 28.2 mmol) was added at ?78° C., the temperature was increased to normal temperature, and the reaction was quenched by the ammonium chloride aqueous solution (aq. NH4C1). After the organic layer was separated, concentration was performed and purification was performed by the chromatography to obtain Structural Formula D-1 (6.1 g, yield 43percent). |