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Product Details of [ 1240963-55-6 ]

CAS No. :1240963-55-6
Formula : C24H18BNO2
M.W : 363.22
SMILES Code : OB(C1=CC=C(C2=CC3=C(C=C2)N(C4=CC=CC=C4)C5=C3C=CC=C5)C=C1)O
MDL No. :MFCD30063200
InChI Key :CFZRUXMJHALVPF-UHFFFAOYSA-N
Pubchem ID :58351149

Safety of [ 1240963-55-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 1240963-55-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 28
Num. arom. heavy atoms 25
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 116.04
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

45.39 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

5.53
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

4.13
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.7
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.97
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.27

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-6.04
Solubility 0.000332 mg/ml ; 0.000000915 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-6.24
Solubility 0.000208 mg/ml ; 0.000000572 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-8.01
Solubility 0.00000356 mg/ml ; 0.0000000098 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-4.59 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.58

Application In Synthesis of [ 1240963-55-6 ]

* 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.

  • Upstream synthesis route of [ 1240963-55-6 ]

[ 1240963-55-6 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 121-43-7 ]
  • [ 1028647-93-9 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: at -78 - 20℃; for 20 h; Inert atmosphere
Stage #2: With hydrogenchloride In tetrahydrofuran; water for 7 h;
Example 2;In this example, an example in which 3-[4-(9-phenanthryl)-phenyl]-9-phenyl-9H-carbazole (abbreviation: PCPPn) represented by Structural Formula (102) in Embodiment 1 is manufactured will be described. Step 1: Synthesis Method of 4-(9-phenyl-9H-carbazol-3-yl)phenylboronic acidInto a 300-mL three-neck flask was put 8.0 g (20 mmol) of the 3-(4-bromophenyl)-9-phenyl-9H-carbazole obtained in Reaction Scheme (F1-2), the atmosphere in the flask was replaced with nitrogen, 100 mL of dehydrated tetrahydrofuran (abbreviation: THF) was then added to the flask, and the temperature was lowered to -78° C. To this mixture, 3.4 mL (30 mmol) of trimethyl borate was added, and the mixture with the trimethyl borate added was stirred at -78° C. for 2 hours and at room temperature for 18 hours. After the reaction, 1M diluted hydrochloric acid was added to this reaction solution until the solution became acid, and the solution with the diluted hydrochloric acid added was stirred for 7 hours. This solution was subjected to ethyl acetate extraction, and an organic layer obtained was washed with a saturated saline. After the washing, magnesium sulfate was added to the organic layer to remove moisture. This suspension was filtrated, and the obtained filtrate was concentrated, and hexane was added thereto. The mixture was irradiated with ultrasonic waves and then recrystallized to give 6.4 g of white powder that was an objective substance in a yield of 88percent. The reaction scheme of Step 1 is shown (F2-1).
88%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 20 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water for 7 h; Inert atmosphere
Step 1: Synthesis of 4-(9-Phenyl-9H-carbazol-3-yl)phenylboronic acid In a 300 mL three-neck flask, 8.0 g (20 mmol) of 3-(4-bromophenyl)-9-phenyl-9H-carbazole was placed, the air in the flask was replaced with nitrogen, 100 mL of dehydrated tetrahydrofuran (abbreviation: THF) was added, and the temperature was lowered to -78 °C. Into this mixture solution, 15 mL (24 mmol) of a 1.65 mol/L n-butyllithium hexane solution was dropped, and the mixture solution with the n-butyllithium hexane solution added was stirred for 2 hours. To this mixture, 3.4 mL (30 mmol) of trimethyl borate was added, and the mixture was stirred at -78 °C for 2 hours and at room temperature for 18 hours. After the reaction, a 1M diluted hydrochloric acid was added to this reaction solution until the solution became acid, and the solution with the diluted hydrochloric acid added was stirred for 7 hours. This solution was subjected to extraction with ethyl acetate, and the obtained organic layer was washed with a saturated aqueous sodium chloride solution. After the washing, magnesium sulfate was added to the organic layer to adsorb moisture. This suspension was filtered, and the obtained filtrate was concentrated, and hexane was added thereto. The mixture was irradiated with supersonic waves and then recrystallized to give 6.4 g of a white powder, which was the object of synthesis, in a yield of 88 percent. A reaction scheme of Step 1 described above is illustrated below. [0360] [0361] The Rf values of the substance that was the object of synthesis and 3-(4-bromophenyl)-9-phenyl-9H-carbazole were respectively 0 (origin) and 0.53, which were found by silica gel thin layer chromatography (TLC) (developing solvent: ethyl acetate/hexane in a 1 :10 ratio). In addition, the Rf values of the object of the synthesis and 3-(4-bromophenyl)-9-phenyl-9H-carbazole were respectively 0.72 and 0.93, which were found by silica gel thin layer chromatography (TLC) using ethyl acetate as a developing solvent.
References: [1] Patent: US2012/77987, 2012, A1, . Location in patent: Page/Page column 43-44.
[2] Patent: WO2013/15144, 2013, A1, . Location in patent: Paragraph 0357-0360.
  • 2
  • [ 1028647-93-9 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2 h; Inert atmosphere
Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 20 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water for 7 h;
Step 2: Synthesis Method of 4-(9-phenyl-9-H-carbazol-3-yl)phenylboronic acidA synthetic scheme for 4-(9-phenyl-9-H-carbazol-3-yl)phenylboronic acid is illustrated in the following (F-2). Into a 300-mL three-neck flask, 8.0 g (20 mmol) of the 3-(4-bromophenyl)-9-phenyl-9H-carbazole obtained in Step 1 described above was put, the atmosphere in the flask was replaced with nitrogen, 100 mL of dehydrated tetrahydrofuran (abbreviation: THF) was then added to the flask, and the temperature was lowered to -78° C. Into this mixture solution, 15 mL (24 mmol) of a 1.65 mol/L n-butyllithium hexane solution was dropped, and the mixture solution with the n-butyllithium hexane solution added was stirred for 2 hours. To this mixture, 3.4 mL (30 mmol) of trimethyl borate was added, and the mixture with the trimethyl borate added was stirred at -78° C. for 2 hours and at room temperature for 18 hours. After the reaction, 1M diluted hydrochloric acid was added to this reaction solution until the solution became acid, and the solution with the diluted hydrochloric acid added was stirred for 7 hours. This solution was subjected to ethyl acetate extraction, and the obtained organic layer was washed with a saturated saline. After the washing, magnesium sulfate was added to the organic layer to adsorb moisture. This suspension was filtrated, and the obtained filtrate was concentrated, and hexane was added thereto. The mixture was exposed to supersonic waves and then recrystallized to obtain an intended white powder with a yield of 6.4 g at 88percent.The Rf value of the intended product obtained by silica gel thin layer chromatography (TLC) (developing solvent, ethyl acetate:hexane=1:10) was 0 (origin), and the Rf value of the 3-(4-bromophenyl)-9-phenyl-9H-carbazole was 0.53. In addition, the Rf value of the intended product obtained by silica gel thin layer chromatography (TLC) using ethyl acetate as the developing solvent was 0.72, and the Rf value of the 3-(4-bromophenyl)-9-phenyl-9H-carbazole was 0.93. In any case of the developing solvents, no spot derived from the 3-(4-bromophenyl)-9-phenyl-9H-carbazole was observed. Therefore, it is determined that the implementation of the reaction in Step 2 provided the intended product with a higher degree of purity in a simple manner with an extremely high yield.In Step 2, the 3-(4-bromophenyl)-9-phenyl-9H-carbazole as a raw material halide was reacted with n-butyllithium whose amount (1.2 equivalents) is larger than that of the 3-(4-bromophenyl)-9-phenyl-9H-carbazole as a lithiating agent so that the raw material halide was not left. In addition, the raw material halide is more likely to dissolve in a nonpolar solvent such as hexane, than the boron compound (4-(9-phenyl-9-H-carbazol-3-yl)phenylboronic acid) as the intended product, and can be thus easily separated by recrystallization. This allows for preventing an impurity from being produced by a coupling reaction between the boron compound (4-(9-phenyl-9-H-carbazol-3-yl)phenylboronic acid) synthesized in Step 2 and a halide (3-(4-bromophenyl)-9-phenyl-9H-carbazole), which was an impurity in the boron compound, in the next step of a reaction with a halogenated anthracene compound.
References: [1] Patent: US2011/172441, 2011, A1, . Location in patent: Page/Page column 16-17.
  • 3
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  • [ 1028647-93-9 ]
  • [ 7732-18-5 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 14 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 20 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexane for 7 h;
A solution of 8.0 g (20 mmol) of 3- (4-bromophenyl) -9-phenyl-9H-carbazole was placed in a 300 mL three-And the gas atmosphere in the flask was replaced with nitrogen. Then, 100 mL of dehydrated tetrahydrofuran (abbreviation: THF) was added,The temperature was set to -78 ° C.And the mixture was added dropwise to the above-mentioned mixed solution1.65mol / LofN-butyllithiumHexane solution (15 mL) was added and stirred for 2 hours.To the above mixture was added trimethyl borate (3.4 mL, 30 mmol), and the mixture was stirred at -78 ° C for 2 hours.And stirred at room temperature for 18 hours. After the reaction, 1M dilute hydrochloric acid was added to the reaction solution until the solution became acidic, and the mixture was stirred for 7 hours. The extract was extracted with ethyl acetate, and the resulting organic layer was washed with saturated brine. After washing, magnesium sulfate was added to the organic layer to adsorb moisture. The suspension was filtered, and the resulting filtrate was concentrated, hexane was added and an ultrasonic wave was applied, followed by recrystallization, and a white powder of the desired product was obtained at a yield of 6.4 g and a yield of 88percent.
References: [1] Patent: TWI565701, 2017, B, . Location in patent: Page/Page column 118; 119.
  • 4
  • [ 854952-58-2 ]
  • [ 1679-18-1 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
85% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 24 h; Inert atmosphere; Reflux Round bottom flask was charged with 9-Phenyl-9H-carbazole-3-boronic acid 15g (52.25mmol), 4-chloro-Phenylboronicacid8.98g (57.47mmol) and the mixture of toluene (174ml) and the mixture was then dissolved in 21.66g of potassium carbonate (156.74 mmol) was added to a stirred aqueous solution of dissolved 87ml. Followed by adding thereto tetrakis triphenylphosphine palladium 1.20g (1.04mmol) was stirred and refluxed for 24 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 (6: 4 by volume) was purified by a silica gel column chromatography to give the intermediate (I) as 16.13g (85percent yield).
85% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 24 h; Inert atmosphere; Reflux Round bottom flask was charged with 9-Phenyl-9H-carbazole-3-boronic acid 15g (52.25mmol), 4-chloro-Phenylboronicacid 8.98g dissolved in an aqueous solution of potassium carbonate 21.66g (156.74mmol) was dissolved was added to (57.47mmol) in toluene (174ml) into theIt was added to 87ml and stirred. Here tetrakistriphenylphosphine palladium was added to 1.20g (1.04mmol) of nitrogen atmosphere It was stirred under reflux for 24 hours under a group. After completion of the reaction, magnesium sulfate, the extract was then extracted with ethyl acetateIt was dried, filtered and concentrated under reduced pressure to the filtrate. Silica gel with: a product n- hexane / dichloromethane (volume ratio 4 6)The desired compound was purified by column chromatography of the intermediate (I) to give a 16.13g (85percent yield).
References: [1] Patent: KR2016/12846, 2016, A, . Location in patent: Paragraph 0207; 0208; 0209.
[2] Patent: KR2016/22081, 2016, A, . Location in patent: Paragraph 0454; 0455; 0456; 0457.
  • 5
  • [ 7647-01-0 ]
  • [ 121-43-7 ]
  • [ 1028647-93-9 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
70%
Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 20℃;
The experimental device is fully dried,In a 1L three-necked flask, 30 g of intermediate A was added.Add 300ml of dry tetrahydrofuranAfter dissolution, the temperature was lowered to -78°C, and 33 ml of 2.5M n-BuLi was added dropwise.After stirring for one hour at the temperature,10.1 g of trimethyl borate was added dropwise at this temperature.After the addition was completed, the mixture was stirred at room temperature overnight.After the reaction is over,Add 4N hydrochloric acid solution,Extract with dichloromethane,The organic phase is washed to neutral with saturated saline solution.dry,Remove the solvent,Purify the crude product with ethyl acetate,The filter cake is the boric acid product.19.2 g of intermediate B with a yield of 70percent.
References: [1] Patent: CN107663214, 2018, A, . Location in patent: Paragraph 0057-0060.
  • 6
  • [ 5419-55-6 ]
  • [ 1028647-93-9 ]
  • [ 1240963-55-6 ]
YieldReaction ConditionsOperation in experiment
31%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h;
Stage #2: at -78 - 20℃; for 17 h;
Stage #3: With water In tetrahydrofuran; ethyl acetate
Preparation of compound 1-2 [152] After dissolving compound 1-1 (17.9 g, 44.8 mmol) in tetrahydrofuran (THF) 200 mL, the mixture was cooled to -78°C, 2.5 M n-butyl lithium (23 mL, 58.3 mmol) was slowly added to the mixture, and the mixture was stirred for 1 hour. Next, isopropyl borate (15.5 mL, 67.2 mmol) was added to the mixture, and the mixture was slowly heated and stirred at room temperature for 17 hours. After completing the reaction, the mixture was extracted with ethylacetate (EA) and H2O, and the EA layer was dried with MgSO4, and concentrated to obtain compound 1-2 (5.02 g, 31 percent).
References: [1] Patent: WO2014/81206, 2014, A1, . Location in patent: Paragraph 151; 152.
  • 7
  • [ 150-46-9 ]
  • [ 1028647-93-9 ]
  • [ 1240963-55-6 ]
References: [1] Patent: CN105601613, 2016, A, . Location in patent: Paragraph 0282; 0283; 0284; 0285.
  • 8
  • [ 589-87-7 ]
  • [ 1240963-55-6 ]
References: [1] Patent: US2012/77987, 2012, A1, .
[2] Patent: WO2014/81206, 2014, A1, .
  • 9
  • [ 854952-58-2 ]
  • [ 1240963-55-6 ]
References: [1] Patent: US2012/77987, 2012, A1, .
[2] Patent: WO2014/81206, 2014, A1, .
  • 10
  • [ 106-37-6 ]
  • [ 1240963-55-6 ]
References: [1] Patent: CN105601613, 2016, A, .
  • 11
  • [ 1153-85-1 ]
  • [ 1240963-55-6 ]
References: [1] Patent: CN105601613, 2016, A, .
  • 12
  • [ 854952-58-2 ]
  • [ 589-87-7 ]
  • [ 1240963-55-6 ]
References: [1] Patent: CN107663214, 2018, A, .
 

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