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Structure of 5400-80-6

Chemical Structure| 5400-80-6

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Product Details of [ 5400-80-6 ]

CAS No. :5400-80-6
Formula : C9H9BrO
M.W : 213.07
SMILES Code : OC1C(Br)CC2=CC=CC=C12
MDL No. :MFCD00003798
InChI Key :RTESDSDXFLYAKZ-UHFFFAOYSA-N
Pubchem ID :95444

Safety of [ 5400-80-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 5400-80-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 48.1
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.82
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

1.93
Log Po/w (WLOGP)?

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

1.72
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.

2.25
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

2.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.03

Water Solubility

Log S (ESOL):?

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

-2.78
Solubility 0.353 mg/ml ; 0.00166 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.

-1.98
Solubility 2.24 mg/ml ; 0.0105 mol/l
Class?

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

Very 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

-3.05
Solubility 0.19 mg/ml ; 0.000891 mol/l
Class?

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

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

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

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

No
Log Kp (skin permeation)?

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

-6.23 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)

2.58

Application In Synthesis of [ 5400-80-6 ]

* 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.

  • Downstream synthetic route of [ 5400-80-6 ]

[ 5400-80-6 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 5400-80-6 ]
  • [ 10485-09-3 ]
YieldReaction ConditionsOperation in experiment
77% With H-β-zeolite; In chlorobenzene; at 120℃; for 6h; General procedure: In a 25 mL round bottomed flask, 250 mg (1.2 mmol) of 2-bromo-1-phenylethanol (1a), 50 mg (20 W/W %) H-β-Zeolite and 1.0 mL of chlorobenzene were placed. The reaction flask was placed in an oil bath at 120C for 6 h; the progress of the reaction was monitored by TLC. After completion of the reaction, the flask was allowed to attain room temperature, and filtered through Watt-Mann filter paper and washed with 10 mL of diethyl ether. Removal of the solvent under reduced pressure, the left out residue was purified by column chromatography on silica gel (200-400 mesh) and hexane as eluent to obtain 2a in (0.16 g) 72% yield.
70% With toluene-4-sulfonic acid; In toluene; at 90℃; for 20h; (2) Synthesis of 2-bromoindene 25 g was taken from the bromohydrin compound obtained from the above reaction, dissolved in 300 mL of toluene, then 500 mg of p-toluene sulfonic acid was added thereto, and the temperature was raised to 90 C., and stirring was carried out for 20 h. After the reactant was cooled to room temperature, it was washed with a sufficient amount of water, dehydrated with MgSO4, and filtered and dried under reduced pressure, thereby obtaining a brown concentrate. This was dissolved in about 100 mL of hexane, and hexane was filtered as an eluent through a silica pad, thereby obtaining non-viscous yellow oil (2-bromoindene) in a yield of 60 to 70%. 1H NMR (500 MHz, CDCl3): δ 3.61 (3H, s), 6.95 (1H, s), 7.18-7.20 (3H, m), 7.27-7.32 (1H, m), 7.39 (1H, m)
60% toluene-4-sulfonic acid; In toluene; for 24h;Heating; Indene (259 mmol, 30 g) and distilled water (9 mL) were put into dimethyl sulfoxide (DMSO, 90 mL), the temperature was decreased to 0C, and N-bromosuccinimide (NBS, 263 mmol, 46.9 g) was slowly added thereto. The temperature of this solution was increased to normal temperature, and the solution was agitated for 12 hours. After that, after the reaction was finished by distilled water, the organic layer was extracted with diethyl ether, and moisture was removed by anhydrous magnesium sulfate. After the filtration under reduced pressure, compound B (38.9 g, 72%) was obtained by removing the solvent by reducing the pressure of the filtered solution and recrystallizing the solution by hexane. 14.3 g of compound B and p-toluenesulfonic acid (p-TsOH, 2.6 mmol, 0.5 g) were dissolved in 60 mL of toluene, and agitated and heated for 24 hours while water was removed by using the Tin-Stock method. Compound C (7.8 g, 60%) was obtained by decreasing the temperature of the solution to normal temperature and using the fractionation method.
40.6 g (88.7%) With p-toluenesulfonic acid monohydrate; In chloroform; toluene; Preparation of 2-Bromoindene To a 500 mL flask containing a magnetic stir bar was added (+/-)trans-2-bromo-1-indanol (50.0 g, 235 mmol), p-toluenesulfonic acid monohydrate (0.50 g, 2.6 mmol), and toluene (300 mL). A Dean Stark trap and reflux condenser were placed on the flask, and the reaction was refluxed for 16 hours. The reaction was transferred to a separatory funnel, chloroform was added (200 mL), and the resulting mixture was washed with aqueous sodium bicarbonate solution (3*200 mL). The organic layer was then washed with a saturated aqueous sodium chloride solution (1*300 mL), dried over anhydrous magnesium sulfate, and filtered. The solvents were removed and distillation provided 40.6 g (88.7 percent) of the slightly yellow crystalline solid collected at 72-105 C. at 3 mm Hg. 1 H NMR (300 MHz, CDCl3, TMS); δ7.4-7.1(m, 4H), 6.93(s, 1H), 3.60(s, 2H). 13 C NMR (75 MHz, CDCl3): δ143.62, 142.22, 132.64, 126.38, 124.59, 124.49, 122.85, 119.88, 45.40. GC-MS: Calculated for C9 H7 79 Br 193.97, found 194.00. Calculated for C9 H7 81 Br 195.90, found 195.90.
With toluene-4-sulfonic acid; In toluene; for 12h;Inert atmosphere; Schlenk technique; Reflux; To a mixture of indene (200mmol), distilled water (15ml) and dimethyl sulfoxide (70ml) was added portion wise an amount of 210mmol of N-bromosuccinimide. The resulting orange solution was stirred for 10h at room temperature, hydrolyzed with chilled water (100ml), and extracted with diethyl ether (3×100ml). The combined extracts were dried with magnesium sulphate and concentrated to give crystals of 2-bromoindan-1-ol upon standing overnight at -24C. The obtained 2-bromoindan-1-ol (120mmol) was suspended in 100ml of toluene and mixed with a catalytic amount of para-toluenesulfonic acid monohydrate. The mixture was heated at reflux for 12h, and water was removed by a Dean-Stark apparatus. The resulting dark brown suspension was filtered and the volatiles were removed under vacuum. The residue was passed through silica gel using pentane as eluent, then the solvent was evaporated, and the crude product was distilled in vacuo. 2-Bromoindene was finally obtained as yellow crystals in 55% yield.

 

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