Structure of 867044-28-8
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CAS No. : | 867044-28-8 |
Formula : | C34H23BO2 |
M.W : | 474.36 |
SMILES Code : | OB(O)C1=CC2=C(C=C1)C(C1=CC3=C(C=CC=C3)C=C1)=C1C=CC=CC1=C2C1=CC2=C(C=CC=C2)C=C1 |
MDL No. : | MFCD11045063 |
InChI Key : | NVPJWLBDGLWXCH-UHFFFAOYSA-N |
Pubchem ID : | 23160220 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 37 |
Num. arom. heavy atoms | 34 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 157.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
9.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
7.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
6.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-8.98 |
Solubility | 0.000000493 mg/ml ; 0.000000001 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-9.82 |
Solubility | 0.0000000713 mg/ml ; 0.0000000002 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-12.87 |
Solubility | 0.0000000001 mg/ml ; 0.0 mol/l |
Class? Solubility class: Log S scale |
Insoluble |
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) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
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 |
-2.75 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 |
1.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.29 |
* 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 |
---|---|---|
61% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux; | 1.7 g (4.9 mmol) of 5-bromo-1,2-diphenyl-1H-benzimidazole, 2.5 g (5.3 mmol) of 9,10-di(2-naphtyl)anthracene-2-boronic acid, and 0.11 g (0.097 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 2.1 g of a greenish white solid (61% yield). Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 698 with respect to a molecular weight of 698.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux; | 1.0 g (2.9 mmol) of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole, 1.5 g (3.2 mmol) of 9,10-di(2-naphtyl)anthracene-2-boronic acid, and 0.067 g (0.058 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 1.7g of a greenish white solid (84% yield) . Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 698 with respect to a molecular weight of 698.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | In an argon atmosphere, 100 mL of dehydrated THF were added to 10 g (20 mmol) of 2-bromo-9,10-di(2-naphtyl) anthracene, and the temperature of the mixture was cooled to -78 C. Then, 14 mL of n-butyllithium (in hexane, 1.6 mol/L) were dropped. After the mixture had been stirred at -78 C for 1 hour, the temperature of the mixture was increased to 0C. The temperature of the mixture was cooled to -78 C again, and 6.6 mL (60 mmol) of trimethoxyborane were added. The mixture was stirred at -78 C for 1 hour, and was then stirred at room temperature for 2 hours. 100 mL of 10-mass% hydrochloric were added, and the whole was stirred for 1 hour, followed by filtration. The resultant solid was washed with toluene to obtain 4.7 g of 9,10-diphenylanthracene-2-boronic acid (50% yield). | |
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; | (9,10-di(naphthalen-2-yl)anthracen-2-yl)boronic acid 2-bromo-9,10-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mL) and cooled to -78 C. At this temperature n-BuLi (2.5M in hexane, 10.2 mL, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stirring for 17 hours the mixture was quenched with HCl, the yellow precipitate was filtered off and washed with water (2*30 mL). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (yield 100%) | |
With hydrogenchloride; n-butyllithium; | (9,10-di(naphthalen-2-yl)anthracen-2-yl)boronic acid Prepared according to procedure described in EP13170862: 2-bromo-9,10-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mL) and cooled to -78 C. At this temperature n-BuLi (2.5M in hexane, 10.2 mL, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stiffing for 17 hours the mixture was quenched with HCl, the yellow precipitate was filtered off and washed with water (2*30 mL). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (100%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; toluene; at 80℃; for 10h; | 2.3 g (6.0 mmol) of 5-(4-chlorophenyl)-1,2-diphenyl-1H-benzimidazole, 3. 1 g (6.6 mmol) of 9,10-di(2-naphthyl)anthracene-2-boronic acid, tris(dibenzylideneacetone)dipalladium (0) (0.14 g, 0.15 mmol), and cesium carbonate (4.7 g, 14 mmol) were suspended into 20 mL of anhydrous dioxane, a solution of tricyclohexylphosphine/toluene (25 mass%, 0.49 ml, 0.43 mmol) was added, and the whole was stirred at 80C for 10 hours. The reaction mixture was diluted with 200 mL of toluene and 100 mL of water, and was filtered through Celite 545 for removing Pd black. An organic layer was fractionated from the filtrate, washed with 50 mL of a saturated sodium chloride solution, and dried with anhydrous magnesium sulfate, and the solvent was distilled off, with the result that red oil was obtained. The oil was purified by means of silica gel column chromatography to obtain 3.2 g of a greenish white solid (69% yield). Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 774 with respect to a molecular weight of 774.30. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Prepared according to procedure described inEP13 2-bromo-9, 1 0-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mE) and cooled to -78 C. At this temperature n-BuEi (2.5M in hexane, 10.2 mE, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stirring for 17 hours the mixture was quenched with HC1, the yellow precipitate was filtered off and washed with water (2x30 mE). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (100%) | |
70% | Synthesis of Intermediate 1c; 5 g of Intermediate 1b (9.81 mmol) was dissolved in 70 ml of THF dried under nitrogen atmosphere, and 4.7 ml of lithium butyl (11.8 mmol) was added to the mixture at -78 C. The mixture was stirred for one hour at the same temperature, and then 2.20 ml of trimethyl borate (29.4 mmol) was added to the mixture. The temperature of the mixture was increased to room temperature, and one hour later, 2N of an aqueous hydrochloric acid solution was added to the mixture and stirred for 3 hours. The obtained solid compound was filtered while being washed with toluene to obtain 3.27 g of light-yellow Intermediate 1c (yield 70%). | |
70% | Synthesis of Intermediate 1c; 5 g of Intermediate 1b (9.81 mmol) was dissolved in 70 ml of THF dried under nitrogen atmosphere, and 4.7 ml of lithium butyl (11.8 mmol) was added to the mixture at -78C. The mixture was stirred for one hour at the same temperature, and then 2.20ml of trimethyl borate (29.4 mmol) was added to the mixture. The temperature of the mixture was increased to room temperature, and one hour later, 2N of an aqueous hydrochloric acid solution was added to the mixture and stirred for 3 hours. The obtained solid compound was filtered while being washed with toluene to obtain 3.27 g of light-yellow Intermediate 1c (yield 70%). |
70% | Synthesis of Intermediate 1c; The intermediate 1b (5g, 9.81 mmol) was dissolved in 70 ml of dried THF under a nitrogen atmosphere, and butyl lithium (4.7ml, 11.8mmol) was added dropwise thereto at -78 C. The reaction mixture was stirred at -78 C for one hour, and trimethylborate (2.20ml, 29.4mmol) was added thereto. The reaction solution was heated to room temperature and incubated for one hour. Then, a 2N HCl solution was added thereto, and the resultant solution was stirred for three hours. The resultant solid compound was washed and filtered with toluene to yield intermediate 1c as a light yellow powder (3.27g, yield: 70%). | |
Synthesis of Intermediate 1c; 5 g (9.81 mmol) of Intermediate 1b was dissolved in 70 ml of dried THF under a nitrogen atmosphere and 4.7 ml (11.8 mmol) of butyl lithium was added thereto at -78C. The resulting product was stirred at the same temperature for 1 hour, and 2.20ml (29.4 mmol) of trimethyl borate was added thereto. The temperature of the mixture was raised to room temperature, a 2N HCl solution was added thereto after 1 hour, and the mixture was stirred for 3 hours. The resulting solid compound was filtered while washing with toluene to obtain 3.27 g of yellow Intermediate 1c (Yield: 70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 6h;Heating / reflux; | Synthesis of Compound 1; 1.85 g of Intermediate 1c (3.90 mmol) and 1 g of Intermediate 1d (3.90 mmol) were added to a mixed solvent of 2.7 g of an aqueous potassium carbonate solution (19.5 mmol) and THF. 225 mg of Pd(PPh3)4 (19.5 mmol) was added to the mixture while the mixture was stirred, and the mixture was refluxed for 6 hours. The mixture was cooled to room temperature, and then the obtained solid compound was filtered while being washed with water, ethanol and THF to obtain 1.73 g of Compound 1 in the form of a pale yellow powder (yield 71%). (1H NMR (400 MHz, CDCl3) 8.13-8.04 (7H), 8.01 (1H), 7.97-7.92 (4H), 7.86-7.82 (2H), 7.75 (2H), 7.71-7.58 (10H), 7.32 (2H), 7.15 (1H), 6.75 (1H)). |
71% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 6h;Heating / reflux; | Synthesis of Compound 1; 1.85 g of Intermediate 1c (3.90 mmol) and 1 g of Intermediate 1d (3.90 mmol) were added to a mixed solvent of 2.7 g of an aqueous potassium carbonate solution (19.5 mmol) and THF. 225 mg of Pd(PPh3)4 (19.5 mmol) was added to the mixture while the mixture was stirred, and the mixture was refluxed for 6 hours. The mixture was cooled to room temperature, and then the obtained solid compound was filtered while being washed with water, ethanol and THF to obtain 1.73 g of Compound 1 in the form of a pale yellow powder (yield 71%). (1H NMR (400MHz, CDCl3) 8.13-8.04 (7H), 8.01 (1H), 7.97-7.92 (4H), 7.86-7.82 (2H), 7.75 (2H), 7.71-7.58 (10H), 7.32 (2H), 7.15 (1H),6.75(1H)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; | SYNTHESIS EXAMPLE 4; Synthesis of Compound 3; Compound 3 was synthesized through Reaction Scheme 4 below: Compound 3 was prepared in the same manner as in Synthesis Example 1, except that Intermediate 3d was used instead of Intermediate 1d. Intermediate 3d was obtained using 2,4'-dibromopropiophenone instead of 2,4'-dibromoacetophenone. 5 g of Intermediate 1c (10.54 mmol) and 2.75 g of Intermediate 3d (9.58 mmol) were subjected to a Suzuki reaction, yielding 4.15 g of Compound 3 in the form of a pale yellow powder (yield 68%). (1H NMR (400 MHz, CDCl3) 8.12 (2H), 8.07-8.02 (5H), 7.97-7.95 (2H), 7.89-7.84 (2H), 7.80-7.71 (4H), 7.70-7.66 (3H), 7.63-7.60 (7H), 7.32 (2H), 7.15 (1H), 6.83 (1H), 2.62 (3H)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; | SYNTHESIS EXAMPLE 3; Synthesis of Compound 7; Compound 7 was synthesized through Reaction Scheme 3 below: Compound 7 was prepared in the same manner as in Synthesis Example 1, except that Intermediate 7d was used instead of Intermediate 1d. Intermediate 7d was obtained using 1-aminoisoquinoline instead of 2-aminopyridine. 10 g of Intermediate 1c (21.08 mmol) and 6.19 g of Intermediate 7d (19.16 mmol) were subjected to a Suzuki reaction, yielding 9.03 g of Compound 7 in the form of a pale yellow powder (yield 70%) (1H NMR (400 MHz, CDCl3) 8.69 (1H), 8.12 (2H), 8.07-8.02 (5H), 7.99-7.95 (4H), 7.89-7.84 (2H), 7.79-7.75 (3H), 7.71-7.65 (4H), 7.64-7.54 (8H), 7.33 (2H), 7.02 (1H)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 6h;Heating / reflux; | Synthesis of Compound 1; The intermediate 1c (1.85g, 3.90mmol) and the intermediate 1d (1g, 3.90mmol) were added to a mixed solvent of a potassium carbonate solution (2.7g, 19.5mmol) and THF, and Pd(PPh3)4 (225mg, 0.196mmol) was added thereto while stirring. The reaction mixture was refluxed for six hours. The reaction solution was cooled to room temperature, and the resultant solid compound was washed with water, ethanol, and toluene, and filtered to yield Compound 1 as a yellow powder (1.73g, yield: 71 %). (1H NMR (400MHz, CDCl3) 8.51 (1H), 8.40(1H), 8.12(1H), 8.06-7.99(5H), 7.96(2H), 7.85(1H), 7.78-7.59(15H), 7.32(2H), 6.84(1H)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 12h;Heating; | Synthesis of Compound 1; 6.0 g (12.63 mmol) of Intermediate 1c and 2.7 g (11.48 mmol) of Intermediate 1d were added to a mixed solvent of 4.76 g (34.4 mmol) potassium carbonate solution and THF, 398 mg (3 mol%) of Pd(PPh3)4 was added thereto while stirring, and the mixture was heated for 12 hours. The mixture was cooled to room temperature and subjected to extraction using dichloromethane. Then, an organic layer was collected, and the solvent was removed by drying the organic layer using anhydrous magnesium sulfate under reduced pressure. The resulting product was filtered using column chromatography (ethyl acetate:dichloromethane=3:7) to obtain 5.3 g of yellow solid Compound 1 (Yield: 80%). 1H NMR (500MHz, CDCl3) delta 8.73(d, 1H), 8.49(d, 1H), 8.18-8.10(m, 5H), 8.05(dd, 2H), 8.01(d, 1H), 7.97(d, 1H), 7.88(d, 1H), 7.84(m, 1H), 7.80-7.62(m, 13H), and 7.36(dd, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; 1,4-dioxane; water; for 12h;Reflux; | 3-3) Synthesis of 2-(2-nitrophenyl)-9,10-di(2-naphthyl)anthracene 10 g (21.1 mmol) of 9,10-dinaphthylanthracene-2-boronic acid, 10.64 g (52.7 mmol) of bromonitrobenzene, 1.21 g (0.05 mmol) of Pd(PPh3)4, and 11.65 g (84.3 mmol) of K2CO3 were diluted with 100 ml of dioxane, 100 ml of THF, and 30 ml of H2O, and then, the mixture was refluxed while heating. After 12 hours, a solvent was removed and the resultant mixture was extracted using MC and washed with a saturated NaCl solution. Then, an organic layer was dried and condensed over MgSO4, and the obtained product was purified by column chromatography (MC/Hex=1/5), thereby producing 2-(2-nitrophenyl)-9,10-di(2-naphthyl)anthracene that was yellow solid (8.4 g, 73%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | 3-2) Synthesis of 2-bromo-9,10-di(2-naphthyl)anthracene 190 g (0.37 mol) of 2-bromo-9,10-di(2-naphthyl)anthracene obtained from 3-1) was dissolved with 1.5 L of THF in a 5L flask and the temperature was cooled to -78C. Then, 279 ml (0.44 mol) of 1.6 M n-BuLi was slowly added dropwise thereto. After one hour, 140 g (0.74 mol) of B(OiPr)3 was slowly added dropwise thereto and the temperature was raised to room temperature and the mixture was stirred. 1 L of 2N HCl(aq) was added to the resultant mixture at a temperature of 0C and then the mixture was extracted using EA. An organic layer was dried over MgSO4 and then re-crystallized with EA/hexane, thereby producing 2-bromo-9,10-di(2-naphthyl)anthracene (150 g, 84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 5h;Reflux; Inert atmosphere; | Example 10: <Synthesis of 9,10-Di(naphthalen-2-yl)-2-[6-(5H-pyrido[4,3-b]indol-5-yl)pyridin-2-yl]anthracene (Compound 30)> In a nitrogen atmosphere, 3.5 g of 9,10-di(naphthalen-2-yl)anthracene-2-boronic acid, 2.2 g of 5-(6-bromopyridin-2-yl)-5H-pyrido[4,3-b]indole, 0.35 g of tetrakistriphenylphosphine palladium, 10 ml of an aqueous 2 M potassium carbonate solution, 40 ml of toluene and 10 ml of ethanol were added to a reaction vessel, then heated under reflux with stirring for 5 hours. After cooling to room temperature, 100 ml of toluene and 100 ml of water were added thereto, followed by stirring, and the organic layer was separated by liquid separation. The organic layer was dried over magnesium sulfate, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (carrier: NH silica gel, eluent: toluene) to obtain 2.2 g (yield: 48%) of 9,10-di(naphthalen-2-yl)-2-[6-(5H-pyrido[4,3-b]indol-5-yl)pyridin-2-yl]anthracene (Compound 30) as a yellow powder. The structure of the obtained yellow powder was identified using NMR. Fig. 10 shows the results of 1H-NMR measurement. The following 31 hydrogen signals were detected on 1H-NMR (CDCl3). delta (ppm) = 9.32 (1H), 8.55 (1H), 8.22 (1H), 8.03-8.13 (8H), 7.85-7.95 (4H), 7.58-7.78 (11H), 7.44 (1H), 7.28-7.35 (3H), 7.21 (1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 8h;Reflux; Inert atmosphere; | Example 6:; <Synthesis of 9,10-Di(naphthalen-2-yl)-2-[4-(5H-pyrido[4,3-b]indol-5-yl)phenyl]anthracene (Compound 12)> In a nitrogen atmosphere, 3.5 g of 9,1 0-di(naphthalen-2-yl)anthracene-2-boronic acid, 2.2 g of 5-(4-bromophenyl)-5H-pyrido[4,3-b]indole, 0.35 g of tetrakistriphenylphosphine palladium, 10 ml of an aqueous 2 M potassium carbonate solution, 40 ml of toluene and 10 ml of ethanol were added to a reaction vessel, then heated under reflux with stirring for 8 hours. After cooling to room temperature, 80 ml of toluene and 20 ml of water were added thereto, followed by stirring, and the organic layer was separated by liquid separation. The organic layer was dried over magnesium sulfate, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (carrier: NH silica gel, eluent: toluene) to obtain 2.4 g (yield: 52%) of 9,10-di(naphthalen-2-yl)-2-[4-(5H-pyrido[4,3-b]indol-5-yl)phenyl]anthracene (Compound 12) as a yellow powder. The structure of the obtained yellow powder was identified using NMR. Fig. 6 shows the results of 1H-NMR measurement. The following 32 hydrogen signals were detected on 1H-NMR (CDCl3). delta (ppm) = 9.36 (1H), 8.48 (1H), 8.19 (1H), 8.14 (2H), 8.05-8.08 (5H), 7.97 (2H), 7.90 (1H), 7.61-7.79 (11H), 7.51 (2H), 7.44 (2H), 7.32-7.37 (3H), 7.30 (1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 5h;Reflux; Inert atmosphere; | Example 8: <Synthesis of 9,10-Di(naphthalen-2-yl)-2-[4'-(5H-pyrido[4,3-b]indol-5-yl)biphenyl-4-yl]anthracene (Compound 43)> In a nitrogen atmosphere, 2.0 g of 9,10-di(naphthalen-2-yl)anthracene-2-boronic acid, 1.5 g of 5-(4'-bromobiphenyl-4-yl)-5H-pyrido[4,3-b]indole, 0.20 g of tetrakistriphenylphosphine palladium, 6 ml of an aqueous 2 M potassium carbonate solution, 23 ml of toluene and 6 ml of ethanol were added to a reaction vessel, then heated under reflux with stirring for 5 hours. After cooling to room temperature, 50 ml of toluene and 20 ml of water were added thereto, followed by stirring, and the organic layer was separated by liquid separation. The organic layer was dried over magnesium sulfate, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (carrier: NH silica gel, eluent: toluene/ethyl acetate) to obtain 1.8 g (yield: 63%) of 9,10-di(naphthalen-2-yl)-2-[4'-(5H-pyrido[4,3-b]indol-5-yl)biphenyl-4-yl]anthracene (Compound 43) as a yellow powder. The structure of the obtained yellow powder was identified using NMR. Fig. 8 shows the results of 1H-NMR measurement. The following 36 hydrogen signals were detected on 1H-NMR (CDCl3). delta (ppm) = 9.39 (1H), 8.52 (1H), 8.22 (1H), 8.13 (2H), 8.04-8.07 (5H), 7.97 (2H), 7.87 (1H), 7.57-7.80 (17H), 7.48 (2H), 7.38 (1H), 7.33 (3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 5.5h;Inert atmosphere; Reflux; | EXAMPLE 3 <Synthesis of 8-[9,10-di(naphthalen-2-yl)-anthracen-2-yl]-5-phenyl-5H-pyrido[4,3-b]indole (compound 78)> Into a nitrogen-purged reaction vessel, 2.0 g portion of the aforementioned 8-bromo-5-phenyl-5H-pyrido[4,3-b]indole obtained in Example 1, 3.5 g of 9,10-di(naphthalen-2-yl)anthracene-2-boronic acid, 0.4 g of tetrakis(triphenylphosphine) palladium, 10 ml of 2 M potassium carbonate aqueous solution, 20 ml of toluene, and 5 ml of ethanol were added and heated, and refluxed for 5.5 hours while stirring. After cooling to room temperature, 50 ml of toluene and 30 ml of water were added thereto, followed by stirring, and thereafter, the organic layer was separated. The organic layer was dehydrated using anhydrous magnesium sulfate and then concentrated under a reduced pressure, to thereby obtain a crude product. The crude product was purified by using a column chromatography (carrier: NH silica gel, eluent: toluene), to thereby obtain 2.2 g (yield 53%) of 8-[9,10-di(naphthalen-2-yl)-anthracen-2-yl]-5-phenyl-5H-pyrido[4,3-b]indole (compound 78) as a yellow powder. Structure of the thus obtained yellow powder was identified using NMR. Results of the 1H-NMR measurement are shown in . The following 32 signals of hydrogen were detected by 1H-NMR (CDCl3). delta (ppm) = 9.32 (1 H), 8.48 (1 H), 8.32 (1 H), 8.11 (2 H), 8.02 - 8.07 (5 H), 7.95 (2 H), 7.88 (1 H), 7.68 - 7.78 (5 H), 7.58 - 7.64 (7 H), 7.49 (3 H), 7.37 (1 H), 7.33 (2 H), 7.24 (1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41.33% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 7.5h;Inert atmosphere; Reflux; | The 5-bromo-2-{4-(pyridin-3-yl)phenyl}-2H-benzotriazole synthesized in Example 1 2.9 g, 9,10-Di(naphthalen-2-yl)anthracen-2-ylboronic acid 4.7 g, 2M Potassium carbonate aqueous solution 12 ml, Toluene 30 ml, Ethanol 5.6 ml, and Tetrakistriphenylphosphine palladium (0) 0.4 g, were put into the reaction vessel purged with nitrogen, and were heated and refluxed for 7.5 hours with stirring. [0135] The organic layer was picked up by the separating operation, concentrated under a reduced pressure and was refined by the column chromatography to obtain 2.4 g of a faintly green powder of 5-{9,10-di(naphthalen-2-yl) anthracen-2-yl}-2-{4-(pyridin-3-yl)phenyl}-2H-benzotriazole (compound 108) (yield, 41.33%). [0136] The obtained faintly green powder was identified for its structure by the NMR. Fig. 10 shows the results of the 1H-NMR measurement. [0137] The following 28 signals of hydrogen were detected by the 1H-NMR (CDCl3). delta (ppm) = 8.91 (1H) 8.63 (1H) 8.42 (2H) 8.13 (2H) 8.06 (5H) 8.03 (1H) 7.96 - 7.60 (17H) 7.40 (1H) 7.34 (2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.5% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 10.5h;Inert atmosphere; Reflux; | Into the reaction vessel with nitrogen purification, nitrogen gas used for mixing with and 60 minutes Furthermore, to add 0.1g four (triphenylphosphine) palladium (0), and mixture with stirring and heating reflux 10.5 hours. Collecting organic layer through the separating operation, concentrated under reduced pressure and refining by column chromatography, to obtain 6.6g of 4 - [4 - [5 - {9,10-di (naphthalene-2-yl) anthracene-2-yl} benzo triazol-2-yl] phenyl] isoquinoline (compound 14) of the yellow powder (yield 88.5%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.8% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 10.5h;Inert atmosphere; Reflux; | Into the reaction vessel with nitrogen purification, nitrogen gas used for mixing with and 60 minutes. Furthermore, to add 0.1g four (triphenylphosphine) palladium (0), and mixture with stirring and heating reflux 10.5 hours. Collecting organic layer through the separating operation, concentrated under reduced pressure and refining by column chromatography, to obtain 6.7g of 3 - [4 - [5 - {9,10-di (naphthalene-2-yl) anthracene-2-yl} benzo triazol-2-yl] phenyl] quinoline (compound 15) of the yellow powder (yield 89.8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Under nitrogen of 2-bromo -9,10- di (naphthalene-2-yl) anthracene ( 10g , 1.0eq ) in THF 150 ml The mixture was after n-BuLi (11.8 ml, 1.5eq) cooled to -78 to It was added slowly and stirred for 1 hour. After adding the trimethyl borate ( 3.2ml , 1.5eq ) to the reaction mixture after 2 hours cooled to 0 back extracted with MC it was added to 6M HCl . The concentrate EA: hexane = 1: 1 column separation to obtain a white solid compound 97-1 . ( 5.5g , 60 % ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 110℃; for 12h; | compound 70-4 ( 3g , 1.1eq ) , compound 97-1 (3.6g, 1.0eq), Pd (PPh3) 4 (0.877g, 0.1eq), K2CO3 (2.0g, 2.0eq) 40 ml 1,4 dioxane / 10 ml H2O and the mixture was stirred for 12 hours at 110 . After filtering the hot reaction given washed with hot 1,4-dioxane to give a yellow solid compound 97 . ( 4.3g , 72 % ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 12h;Inert atmosphere; Reflux; | Under nitrogen compound 179-2 ( 12.6g , 1.0eq ) , 9,10- di ( naphthalen-2-yl) anthracene -2-yl boronic acid ( 9,10 - di ( naphthalen - 2 - yl ) anthracen - 2- yl boronic acid) (15.1g, 1.2eq), Pd (PPh3) 4 (4.02g, 0.1eq), refluxed for 12 hours, the toluene 200 ml / 50ml ethanol / H2O mixture of 30 ml K2CO3 ( 7.35g , 2.0eq ) It was stirred . After the reaction product was filtered in a hot state to a hot wash given 1,4-dioxane to give a yellow solid compound 179 . (8.52g, 45%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In ethanol; water; toluene; for 12h;Reflux; | The compound is added 10-1 (6.23g, 12 . 3mmol), 9,10-di (2-naphthyl) anthracene-2-boric acid (7.51g, 14 . 7mmol), Pd (PPh3)4(0.71g, 0 . 615mmol), 2M K2CO3aqueous solution (45 ml), toluene (250 ml) and ethanol (45 ml), and then reflux 12 hours. After the completion of reaction, the resulting reaction product is cooled to the room temperature, distilled water and is then used to extract the EA. Organic layer using an anhydrous MgSO4drying, and the post for rotary evaporimeter to remove the solvent, the use of methylene chloride and hexane as a solvent through the column chromatography purification of the resulting reaction product, obtaining 5.4g (56%) the target compounds 10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium phosphate; bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; for 4h;Reflux; | [Formula 2-A] (10g, 37.2mmol) and (9,10-di(naphthalene-2-yl) anthracene-2-yl) boronic acid (17.7g, 37.2mmol) wasadded to dioxane 150mL, a K3PO4 23g ,itwas dissolved in water 50mL.After input a Pd (Pt-Bu3) 2 0.3g refluxed stirring for four hours.fter cooling to roomtemperature, the resulting solid was filtered.The filtered solids were subjected to chloroform ethanolrecrystallization was prepared [Formula 1-6] (18.3g, 74% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.1% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 22h;Reflux; Inert atmosphere; | M = 1, X = C(1-1), (A-1), (A-5)To a solution of 3.0 g of the second intermediate halide synthesized in Example 1 <strong>[867044-28-8]{9,10-bis(naphthalen-2-yl)anthracene-2-yl}boronic acid</strong> 6.2 gA 2M aqueous potassium carbonate solution (11 ml)44 ml of toluene11 ml of ethanol0.1 g of tetrakistriphenylphosphine palladium (0)The reaction vessel was purged with nitrogen and heated to reflux with stirring for 22.0 hours.The organic layer was collected by separating operation, concentrated under reduced pressure, and purified by column chromatography to obtain 5- {9,10-bis (naphthalene)Yl} anthracene-2-yl} -2- {4- (pyridin-3-yl) phenyl} -2H-naphtho [1,2- d] [1,2,3] triazole 75)(Yield: 56.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54.3% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 12h;Reflux; Inert atmosphere; | 6.2 g of 2-M potassium carbonate aqueous solution 11 ml of toluene 44 ml of ethanol 11 ml of tetraquistriphenylphosphorus tetrakis (triphenylphosphine) palladium The reaction mixture was heated under reflux for 14.0 hours while being stirred with stirring in a nitrogen-purged reaction vessel of finadium palladium (0). The organic layer was collected by separating, concentrated under reduced pressure, and purified by column chromatography to obtain 5- { 2-yl] -2- {4- (pyridin-2-yl) phenyl} -2H-naphtho [ 3.04 g (yield: 54.3%) of pale green powder of triazole (Compound 77) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 8h;Reflux; | 5.0 g of 9-bromo-6-phenyl-6H-indolo [2,3-b] quinoxaline, 9,10-di (naphthalen- 2-yl) anthracen-2-ylboronic acid 7. , 0.8 g of tetrakis (triphenylphosphine) palladium, 20 ml of a 2 M potassium carbonate aqueous solution, 80 ml of toluene and 20 ml of ethanol were added and heated,While refluxing for 8 hours. After cooling to room temperature, 20 ml of water was added, followed by stirring, and a crude product was obtained by filtration. 1,2-Dichlorobenzene was added to the crude product, heated and dissolved, NH silica gel was added and stirred, then the filtrate was collected by filtration and concentrated. The resulting concentrate was subjected to crystallization purification using a mixed solvent of 1,2-dichlorobenzene / methanol to give 9- {9,10-di (naphthalen-2-yl) anthracen-2-yl} - 6-phenyl-6H-indolo [2,3-b] quinoxaline 5.6 g (yield 58%) of a yellow powder of (compound 2) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; at 95℃;Inert atmosphere; | General procedure: General procedure for Suzuki coupling reactions A 100-m L, two-necked, round-bottomed flask equipped with a stirring bar, a stopper and a reflux condenser fitted with a nitrogen inlet is charged with (6.8mmol) boron ic ester and benzimidazole-derivative (1) or (2) (7,74mmol, 1 . 14 eq ). The atmosphere is replaced by argon, deoxygenated glyme (35 ml ), 2M aqueous solution of potassium carbonate ( 12 ml, 3.5 eq, deoxygenated by passing argon stream through the solution for 30 min ), and tetrakis(triphenylphosphin)paiiadium(0) (0.204mmol, 0.03eq) are added in this order. The flask is sealed, the mixture is stirred under argon at 95C overnight. Aqueous solution of sodium sodium d i e t h yl c a b a m o d i t h i o a t c sodium diethylcarbamodithioatc trihydrate (3%, 50ml ) is added and the mixture is stirred for 30m in at RT. A heterogeneous mixture is poured into 10 fold excess of water, a precipitated product is col lected by filtration using a sintered glass filter, washed on the filter with water (3x20 ml ) and methanol (2x 20ml ) and dried in vacuum at RT. Crude product is then purified by re-crystallization or by column chromatography. l-(3-(9 0-di(naphthalen-2-yl)anthracen-2-yl)phenyl)-2-(pyridin-2 Obtained using general Suzuki coupling procedure from (9,10-di(naphthaien-2- yi)anthracen-2-yl)boronic acid and 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 80℃;Inert atmosphere; | 1000ml a bottle,With magnetic stirring,A solution of 5.68 g (molecular weight: 284, 0.02 mol) of 3-bromo-7-phenyl-1,5-naphthyridine,(Molecular weight: 474, 0.022 mol) of 9,10-bis (naphthalen-2-yl) anthracene-2-boronic acid,Tetrakis (triphenylphosphine) palladium (molecular weight: 1154, 0.001 mol)2M sodium carbonate aqueous solution 80ml, toluene 80ml, ethanol 80ml.After refluxing with argon, reflux was carried out at 80 C and the reaction was monitored by thin layer chromatography (TLC)3.5 hours after TLC found that the raw material bromine reaction is complete, only the product point.Cooling, separating the organic layer, drying, column chromatography, ethyl acetate / petroleum ether leaching,To give 11.33 g of the compound represented by the formula (14) having a molecular weight of 634 and a yield of 89.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.4% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; for 4h;Inert atmosphere; Reflux; | 1000 ml three bottles,With magnetic stirring,Nitrogen protection,4.72 g (molecular weight: 236, 0.02 mol) of 6-bromo-2,3-dimethylquinoxaline was added,(Molecular weight: 474, 0.022 mol) of 9,10-bis (naphthalen-2-yl) anthracene-2-boronic acid,Tetrakis (triphenylphosphine) palladium (molecular weight: 1154, 0.001 mol)2M aqueous sodium carbonate solution 80ml,Toluene 80ml,Ethanol 80ml.After argon replacement,Reflux,The reaction was monitored by thin layer chromatography (TLC). After 4 hours, the TLC found that the bromide reaction was complete and only the product point was obtained. Cooling to 25 C, separating the organic layer, drying, column chromatography, ethyl acetate / petroleum ether leaching,To obtain 11.7 g of the compound represented by the formula (12), having a molecular weight of 586 and a yield of 87.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.7% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; for 4.5h;Inert atmosphere; Reflux; | 1000 ml three bottles, with magnetic stirring,Nitrogen protection,5.16 g of 2-bromophenazine (molecular weight 258, 0.02 mol) was added,(Molecular weight: 474, 0.022 mol) of 9,10-bis (naphthalen-2-yl) anthracene-2-boronic acid,Tetrakis (triphenylphosphine) palladium (molecular weight: 1154, 0.001 mol)2M aqueous sodium carbonate solution 80ml,Toluene 80ml, ethanol 80ml.After argon replacement, reflux,The reaction was monitored by thin layer chromatography (TLC)4.5 hours after TLC found that the raw material bromine reaction is complete,Only the product point.Cooling, separating the organic layer,Evaporated to dryness, column chromatographic separation,Ethyl acetate / petroleum ether leaching,To obtain 9.94 g of the compound represented by the formula (12)Molecular weight 608, yield 81.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | (4-(9,10-di(naphthalen-2-yl)anthracen-2-yl)phenyl)diphenylphosphine oxide (B1) According to general procedure B Known from WO2012/173370 (LG, paragraph 131) (4-bromophenyl)diphenylphosphine oxide: 1.88 g (5.3 mmol, 1.0 eq) <strong>[867044-28-8](9,10-di(naphthalen-2-yl)anthracen-2-yl)boronic acid</strong>: 3.0 g (6.3 mmol, 1.2 eq) Pd(PPh3)4: 183 mg (0.16 mmol, 3 mol. %) K2CO3, 2M: 8 mL DME: 20 mL Column chromatography: SiO2, ethyl acetate Yield: 3.0 g (81%) yellow solid mp: n.a. (glassy) EI-MS: m/z=706 1H NMR (CD2Cl2, 25 C.): delta=7.32 (m, 2H); 7.44 (m, 4H); 7.53 (m, 2H); 7.63 (m, 15H); 7.75 (m, 2H); 7.85 (d, J=1.8 Hz, 1H); 7.94 (m, 2H); 8.04 (m, 5H); 8.11 (d, J=1.8 Hz, 2H) ppm. 13C NMR (CDCl3, 25 C.): delta=144.83; 144.80; 138.33; 137.70; 136.86; 136.80; 136.77; 134.05; 134.04; 133.89; 133.47; 133.44; 133.06; 133.02; 132.94; 132.60; 132.48; 132.40; |