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Structure of 667940-23-0

Chemical Structure| 667940-23-0

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Product Details of [ 667940-23-0 ]

CAS No. :667940-23-0
Formula : C16H11Br
M.W : 283.16
SMILES Code : BrC1=CC(C2=CC=C3C=CC=CC3=C2)=CC=C1
MDL No. :MFCD16658911
InChI Key :FWPXWVYUNHYGPE-UHFFFAOYSA-N
Pubchem ID :23080773

Safety of [ 667940-23-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 667940-23-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 16
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 77.08
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.03
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

6.1
Log Po/w (WLOGP)?

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

5.27
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.

5.35
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

5.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.0

Water Solubility

Log S (ESOL):?

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

-6.07
Solubility 0.000242 mg/ml ; 0.000000853 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.

-5.88
Solubility 0.000372 mg/ml ; 0.00000131 mol/l
Class?

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

Moderately 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

-7.44
Solubility 0.0000103 mg/ml ; 0.0000000365 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

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
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

Yes
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

No
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

No
Log Kp (skin permeation)?

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

-3.7 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

1.0
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

2.0
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

0.0 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<1.0
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)

1.97

Application In Synthesis of [ 667940-23-0 ]

* 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.

  • Downstream synthetic route of [ 667940-23-0 ]

[ 667940-23-0 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 591-18-4 ]
  • [ 32316-92-0 ]
  • [ 667940-23-0 ]
YieldReaction ConditionsOperation in experiment
85% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 24h;Heating / reflux; 2- A. Production of compound 2a; [79] After l-bromo-3-iodobenzene (10 g, 35.35 mmol) and 2-naphthalene bromic acid(5.47 g, 31.82 mmol) were dissolved in anhydrous THF (100 mL), Pd(PPh ) (1.2 g, 1.06 mmol) and 50 mL of 2M K CO aqueous solution were added and then refluxed <n="17"/>for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2a (8.5 g, 85%).[80] MS [M + H] = 283
76% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 24h;Inert atmosphere; Reflux; Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthaleneboronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine)palladium(0), 6.4 L of toluene and 3.2 L of aqueous solution of 2M sodium carbonate were added together, and stirred while being refluxed for 24 hours. After the reaction was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was washed by water and dried with magnesium sulfate, the toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2-(3-bromophenyl)naphthalene was obtained at an yield of 76%.
  • 2
  • [ 667940-23-0 ]
  • [ 624744-67-8 ]
  • C50H32 [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 24h;Heating / reflux; 2-B . Production of compound 2; [82] After the compound 2a (4.0 g, 14.13 mmol) and the compound Id (9.43 g, 16.95 mmol) were dissolved in anhydrous THF (200 mL), Pd(PPh ) (0.49 g, 0.42 mmol) and 60 mL of 2M K CO aqueous solution were added and then refluxed for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2 (6.0 g, 67%) represented by Formula 1-2. MS data in respects to the compound 2 are shown in Fig. 3.[83] MS [M + H] = 632
  • 3
  • [ 667940-23-0 ]
  • [ 911390-71-1 ]
  • C46H30 [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% (1) Synthesis of Compound 2-1 Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthalene boronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine) palladium(0), 6.4 L of toluene and 3.2 L of 2M sodium carbonate solution were mixed together, and stirred for 24 hours while being refluxed. After the reaction in the mixture was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was cleansed by water and dried with magnesium sulfate, toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2(3-bromophenyl)naphthalene was obtained with an yield of 76%.
75% Synthesis Example 6 (Synthesis of 2-(3-bromophenyl)naphthalene) The same procedures as those conducted in Synthesis Example 2 were conducted except that 3-iodobromobenzene was used in place of 4-iodobromobenzene, and 20.1 g of a colorless oily substance was obtained. Since m/z=284 and 282 in FD-MS of the obtained compound, which corresponded to C16H11Br=283, the compound was identified to be 2-(3-bromophenyl)naphthalene (the yield: 75%).
  • 5
  • [ 108-36-1 ]
  • [ 32316-92-0 ]
  • [ 667940-23-0 ]
YieldReaction ConditionsOperation in experiment
47% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 24h;Heating / reflux; Example 13 : Preparation of compound 30; [196][197] 13-A. Preparation of compound 13a[198] Under N atmosphere, 1,3-dibromophenyl (10 g, 42.2 mmol), 2-naphthyl boronic acid (5.16 g, 42.2 mmol), and Pd(PPh ) (2.4 g, 2.1 mmol) were added to a 2 M aqueous solution of potassium carbonate (50 mL) and THF (300 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, dried over magnesium sulfate, and distilled under reduced pressure. The resultant was purified by column chromatography to prepare a compound 13a (4.6 g, 47%). MS [M] = 233
  • 6
  • [ 667940-23-0 ]
  • [ 870774-29-1 ]
YieldReaction ConditionsOperation in experiment
67% Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of <strong>[667940-23-0]2(3-bromophenyl)naphthalene</strong> and 3 L of dehydrated TI-IF was cooled down to minus 10 degree C., and 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium was dropped into the mixture while the mixture was being stirred. Then, the mixture was stirred at 0 degree C. for 2 hours. The reaction solution was again cooled down to minus 78 degrees C., and 450 g (2.39 mol) of triisopropylborate was dropped into the solution. Then, the solution was stirred at room temperature for 17 hours. The reaction mixture was added with aqueous solution of hydrochloric acid and stirred at room temperature for 1 hour. The reaction mixture was added with 3 L of toluene, and aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl)phenylboronic acid was obtained at an yield of 67%.
50% 13-B. Preparation of compound 13b; [200] Under N atmosphere, to a compound 13a (4 g, 14.1 mmol) prepared in 13-A, dehydrated ether (80 mL) and dehydrated toluene (80 mL) were added, and cooled to - 640C in ice bath. A 2.5 M butyl lithium/hexane solution (6 mL) was added drop wise thereto for 30 minutes, and subjected to reaction at -640C for 2 hours. Boronic acid triisoester (9 mL) was added dropwise thereto for 15 minutes, and then stirred at room <n="75"/>temperature for 12 hours. After ice cooling, 2 N hydrochloric acid (35 rnL) was added at 1O0C or lower and toluene (10 mL) was added. The mixture was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was re- crystallized from EtOH to prepare a compound 13b (1.75 g, 50%).
  • 7
  • [ 667940-23-0 ]
  • [ 5419-55-6 ]
  • [ 870774-29-1 ]
YieldReaction ConditionsOperation in experiment
67% With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; toluene; (2) Synthesis of Compound 2-2 Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of 2(3-bromophenyl) naphthalene and 3 L of dehydrated THF was cooled down to -10 degrees C., and added with 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium in drops while being stirred. Then, the reaction mixture was stirred for two hours at 0 degree C. The reaction solution was further cooled down to -78 degrees C., and added with 450 g (2.39 mol) of triisopropyl borate in drops. Subsequently, the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was further added with solution of hydrochloric acid to be stirred for one hour at room temperature. The reaction mixture was further added with 3 L of toluene, so that aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl) phenylboronic acid was obtained at an yield of 67%.
  • 8
  • [ 667940-23-0 ]
  • [ 1066-54-2 ]
  • trimethyl((3-naphthalene-2-yl)phenyl)silane [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 0 - 20℃; for 4h;Inert atmosphere; Under an argon gas atmosphere, a mixture of 25.0 g (88.3 mmol) of <strong>[667940-23-0]2-(3-bromophenyl)naphthalene</strong>, 2.17 g (1.77 mmol) of PdCl2(PPh3)2, 0.67 g (3.53 mmol) of CuI and 120 mL of triethylamine was cooled down to 0 degree C., and added with 10.41 g (106 mmol) of trimethylsilylacetylene. Then, the mixture was stirred at room temperature for 4 hours. After the reaction was over, insoluble matters were removed by filtration, and the solvent was distilled away. The obtained residue was added with aqueous solution of hydrochloric acid, and extracted with toluene. After liquid separation, organic phase thereof was washed with aqueous solution of sodium hydrogencarbonate, and subsequently washed with water and saturated sodium chloride solution. The organic phase was dried with anhydrous sodium sulfate. After filtration, the solvent was distilled away. Then, the residue was refined by column chromatography, so that 19.0 g of trimethyl((3-naphthalene-2-yl)phenyl)ethynyl)silane was obtained at an yield of 72%.
  • 9
  • [ 91-20-3 ]
  • [ 1469819-22-4 ]
  • [ 667940-23-0 ]
  • 11
  • bis(3-bromophenyl)iodonium tetrafluoroborate [ No CAS ]
  • [ 667940-23-0 ]
  • 12
  • [ 667940-23-0 ]
  • 9-bromo-11H-benzo[a]carbazole [ No CAS ]
  • C32H20BrN [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With potassium phosphate; copper; In N,N-dimethyl-formamide;Reflux; 9-bromo-11H-Benzo [a] carbazole 20g (67.53mmol), 2 - (3-bromophenyl)-naphthalene 19.1g (67.53mmol), K3PO421.50g (101.30mmol), Cu powder 6.4g (101.30mmol), the dimethylformamide was stirred under reflux using a mid-100ml. after cooling to room temperature, was filtered to remove the catalyst and the K3PO4. To give the compound 46-a 27.9g (59.43mmol, 88% yield) using a reduced pressure was purified by column chromatography and dried
  • 13
  • [ 667940-23-0 ]
  • C38H24N2O2 [ No CAS ]
  • 14
  • [ 667940-23-0 ]
  • C38H24N2 [ No CAS ]
  • 15
  • [ 667940-23-0 ]
  • N-(2-(4-isopropylpiperazin-1-yl)ethyl)-1-(3-(naphthalen-2-yl)phenyl)piperidin-4-amine [ No CAS ]
  • 16
  • [ 667940-23-0 ]
  • tert-butyl (2-(4-isopropylpiperazin-1-yl)ethyl)(piperidin-4-yl)carbamate [ No CAS ]
  • tert-butyl (2-(4-isopropylpiperazin-1-yl)ethyl)(1-(3-(naphthalen-2-yl)phenyl)piperidin-4-yl)carbamate [ No CAS ]
  • 17
  • [ 667940-23-0 ]
  • [ 33104-32-4 ]
  • 18
  • [ 667940-23-0 ]
  • [ 176034-11-0 ]
  • 19
  • [ 667940-23-0 ]
  • [ 677-22-5 ]
  • 2-(3-(tert-butyl)phenyl)naphthalene [ No CAS ]
  • C20H20 [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With nickel chloride hydrate; at -10℃; for 0.5h; General procedure: To a mixture of aryl halide (0.3 mmol), NiCl2(H2O)1.5 [1] (0.0075 mmol, 2.5 mol %), was charged dry THF (1 mL). The mixture was pumped and refilled with nitrogen for three times. The resulting mixture was stirred at -10 under nitrogen for 30 min. The reaction mixture was quenched through the addition of ice MeOH, then poured into a separatory funnel containing saturated aqueous NH4Cl (ca. 5 mL) and extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine and dried over Na2SO4. The crude product was purified by column chromatography. Extent of isomerization can be easily determined via 1H NMR spectroscopy by comparison of the intergral of the singlet from the t-butyl group (1.3-1.4 ppm, 9H) to the integral of the doublet from the benzylic S3 protons of the i-butyl group (2.4-2.5 ppm, 2H). The doublet from the methyls of the i-butyl group could additionally be used (ca. 0.8 ppm, 6H).
  • 20
  • [ 597554-03-5 ]
  • [ 667940-23-0 ]
  • [ 667940-36-5 ]
YieldReaction ConditionsOperation in experiment
53% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; toluene;Reflux; General procedure: In a round-bottom flask, 37.3 g (132 mmol) of 1-bromo-4-iodobenzene, 14.2 g (125 mmol) of (1H-1,2,4-triazol-1-yl) boronic acid,Potassium carbonate 36.6g (264mmol), Pd (PPh3) 4 3g (2mmol), water 70ml, toluene 180ml and tetrahydrofuran 180ml was added and refluxed.After the reaction, the layer was separated to remove the aqueous layer and the organic layer was concentrated under reduced pressure.Column chromatography was used to obtain 22 g of 1- (4-bromophenyl) -1H-1,2,4-triazole (75% yield).
 

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