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Structure of 4106-66-5

Chemical Structure| 4106-66-5

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Product Details of [ 4106-66-5 ]

CAS No. :4106-66-5
Formula : C12H9NO
M.W : 183.21
SMILES Code : NC1=CC2=C(C=C1)C1=CC=CC=C1O2
MDL No. :MFCD00092339
InChI Key :GHQCIALFYKYZGS-UHFFFAOYSA-N
Pubchem ID :20061

Safety of [ 4106-66-5 ]

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

Computational Chemistry of [ 4106-66-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 13
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 58.12
TPSA ?

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

39.16 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.98
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

3.44
Log Po/w (WLOGP)?

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

3.18
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.

2.17
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

2.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.7

Water Solubility

Log S (ESOL):?

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

-3.83
Solubility 0.0271 mg/ml ; 0.000148 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.94
Solubility 0.0209 mg/ml ; 0.000114 mol/l
Class?

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

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

-4.6
Solubility 0.00457 mg/ml ; 0.0000249 mol/l
Class?

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

Moderately 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

No
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

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

Yes
Log Kp (skin permeation)?

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

-4.98 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<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)

2.46

Application In Synthesis of [ 4106-66-5 ]

* 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 [ 4106-66-5 ]

[ 4106-66-5 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 4106-66-5 ]
  • [ 39213-20-2 ]
  • 3,5-dibromo-benzenesulfonic acid dibenzofuran-3-ylamide [ No CAS ]
  • 2
  • [ 4106-66-5 ]
  • [ 599-91-7 ]
  • dibenzofuran-3-yl-propyl-amine [ No CAS ]
  • 3
  • [ 4106-66-5 ]
  • [ 26608-06-0 ]
YieldReaction ConditionsOperation in experiment
68% To a 500 mL four-necked round bottom flask equipped with a stirrer, a Liebig condenser (not required), a thermometer, and a 200 mL dropping funnel, 19.0 g (102.6 mmol) of the amino compound obtained in the above ,190 mL of water and 57 mL of 48% hydrobromic acid were added and stirred overnight. Subsequently, the solution was cooled to -10 C. in an ice water bath, and a solution of 8.1 g (117.4 mmol) of sodium nitrite dissolved in 150 mL of water was added dropwise under conditions such that the temperature did not rise by 5 C. or more, and the diazotized The reaction solution was stirred at 5 C. or less for 1 hour to obtain a diazonium solution.Next, in a 1 L four-necked round bottom flask equipped with a stirrer, an Erlin condenser, a thermometer, and a 500 mL dropping funnel, 16.2 g (116.9 mmol) of cuprous bromide, 48% hydrobromic acid 38 mL and water 90 mL were added, and the mixture was cooled to 0 C. and stirred. Subsequently, the diazonium solution was added dropwise at a temperature not exceeding 5 C. and stirred at the same temperature for 30 minutes, then the temperature was raised to 40 C., and the mixture was stirred at the same temperature for 18 hours.200 mL of water was added to the obtained reaction solution, cooled to room temperature, and extracted twice with 200 mL of DCM. Then, the organic layer was washed with 100 mL of 5% sodium sulfite aqueous solution, then washed with 100 mL of saturated brine, dried with magnesium sulfate, magnesium sulfate was removed by suction filtration, and the solvent was distilled off under reduced pressure. Subsequently, the resulting crude product was purified by silica gel column chromatography using n-heptane as a developing solution to obtain 17.2 g (yield: 68.0%) of the desired bromide.
67% Sodium nitrite (4.4 g, 65 mmol) was dissolved in 40 ml of concentrated sulfuric acid at 0 C, and compound M-2 (10.6 g, 58 mmol) was dissolved in a small amount of glacial acetic acid and slowly dropped into the reaction solution to maintain the temperature. Below 5 C, after the completion of the dropwise addition, the temperature was kept at 0 C and stirring was continued for 2 hours. Diethyl ether (200 ml) was added to the reaction mixture for stirring, and a diazonium salt was precipitated and filtered to obtain a brown solid; another reaction flask was added with CuBr (12.5g, 87mmol), 48% HBr (300ml), Finally, the obtained brown diazonium salt is added, warmed to 66 C for 2 hours, cooled to room temperature, filtered, filter cake washed twice with water, the obtained solid Petroleum ether: Eluent of dichloromethane = 10:1 was passed through the column to afford intermediate (9.6 g, 67%).
Example 11 3-Bromodibenzofuran Combine N-dibenzofuran-3-ylamine (2.0 g, 10.8 mmol), water (20 ml), and conc. hydrobromic acid (6 ml). Cool to 0 C. Add a solution of sodium nitrite (0.7 g, 10.8 mmol) in water (16 ml). After 15 minutes add the mixture above to a mixture of copper bromide (1.7 g, 12.3 mmol) in water (9.2 ml) and hydrobromic acid (4 ml). Warm to ambient temperature. After 18 hours, add water and extract with dichloromethane, Combine the organic layers and wash sequentially with distilled water and brine and then dry (Na2SO4), filter, and concentrate to give a residue. Chromatograph the residue eluting with 8:2 hexane:EtOAc to give the title compound.
9.6 g Sodium nitrite (4.4g, 65mmol) was dissolved in 40ml when concentrated sulfuric acid, 3-amino-dibenzofuran (10.6g, 58mmol) was dissolved in a small amount of glacial acetic acid was slowly added dropwise to the reaction mixture, maintaining the temperature below 5 , 0 dropwise after incubation was continued stirring for 2 hours, 200ml of diethyl ether was added to the reaction solution was stirred with a diazonium salt and precipitation was filtered to give a brown solid; the other reaction flask was added CuBr (12.5g, 87mmol) , 300ml48% of HBr, brown diazonium salt was added last, temperature was raised to 66 deg.] C for 2 hours, cooled to room temperature, filtered, the filter cake washed twice with water, the resulting solid with petroleum ether: dichloromethane = 10: 1 eluent through the column, to give 9.6g solid

  • 4
  • [ 4106-66-5 ]
  • [ 28785-06-0 ]
  • Dibenzofuran-3-yl-[1-(4-propyl-phenyl)-meth-(E)-ylidene]-amine [ No CAS ]
  • 5
  • [ 540-80-7 ]
  • [ 4106-66-5 ]
  • [ 7789-45-9 ]
  • [ 26608-06-0 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; Step (a) 3-Bromo-dibenzofuran 3-Amino-dibenzofuran (15 g, 81.9 mmoles) was added in portions to a suspension of cupric bromide (21.9 g, 98.2 mmoles) and tert.-butyl nitrite (12.66 g, 122.8 mmoles) in 350 mL of acetonitrile. This mixture was heated to reflux for 2 hours and then stirred for 16 hours at room temperature. The reaction was partitioned between 1 M HCl and diethyl ether. The diethyl ether layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give an oily solid. Chromatography gave the title compound as a yellowish solid.
  • 6
  • [ 26608-06-0 ]
  • [ 4106-66-5 ]
YieldReaction ConditionsOperation in experiment
81% With ammonium hydroxide; copper; In toluene; at 110℃; for 12h;Inert atmosphere; Under a nitrogen stream , 3-bromo- dibenzo [b, d] furan (7.41g, 30.0mmol)It was dissolved in THF100ml, 28% aqueous ammonia (10.2ml, 150mmol) And put Cu a (0.10g, 5mol%), and the mixture was stirred for 12 hours at 110 . The completion of the reactionAfter , and extracted with methylene chloride , put MgSO4 , and filtered . Soluble of the filtered organic layerAfter removing the medium , column chromatography rectification (hexane :: EA = 10 1 (v / v))By Seisuru thing , dibenzo [b, d] furan -3-amine 4.45 g ( yield: 81% ) .
81% With ammonium hydroxide; copper; In tetrahydrofuran; at 110℃; for 12h;Inert atmosphere; The 3-bromodibenzo [b, d] furan (7.41 g, 30.0 mmol) under nitrogen gas stream, After dissolving in 100 ml of THF, 28% aqueous ammonia (10.2 ml, 150 mmol) and Cu (0.10 g, 5 mol%) was added,Followed by stirring at 110 DEG C for 12 hours.After completion of the reaction, the mixture was extracted with methylene chloride, and the mixture was filtered through MgSO4.After removal of the solvent of the filtered organic layer, column chromatography D] benzo [b, d] furan-3-amine (Hexane: EA = 10: 1 (v / v)4.45 g (yield: 81%) was obtained.
  • 7
  • [ 26608-06-0 ]
  • [ 4106-66-5 ]
  • N-(3-dibenzofuranyl)-3-dibenzofuranamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 5h;Inert atmosphere; Reflux; Under argon atmosphere5.0 g of 3-aminodibenzofuran, 6.7 g of <strong>[26608-06-0]3-bromodibenzofuran</strong>,(Bis (dibenzylideneacetone) palladium (0)),1.1 g of tri-tert-butylphosphine,3.9 g of sodium tert-butoxide was added, and the mixture was heated under reflux in 140 mL of toluene for 5 hours.After air cooling, water was added thereto, the organic layer was separated, dried over magnesium sulfate,The solvent was distilled.The obtained crude product was purified by silica gel column chromatography (toluene / hexane mixed solvent) to obtain 8.3 g of Intermediate G (yield: 87%).
  • 8
  • [ 26608-06-0 ]
  • [ 4106-66-5 ]
  • C58H34N2O4 [ No CAS ]
 

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