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Chemical Structure| 6134-54-9 Chemical Structure| 6134-54-9
Chemical Structure| 6134-54-9

5-Bromo-2,3-dihydro-1H-indene

CAS No.: 6134-54-9

4.5 *For Research Use Only !

Cat. No.: A924883 Purity: 95%

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Product Details of [ 6134-54-9 ]

CAS No. :6134-54-9
Formula : C9H9Br
M.W : 197.07
SMILES Code : BrC1=CC2=C(CCC2)C=C1
MDL No. :MFCD09842508
Boiling Point : No data available
InChI Key :UMEFRXDFDVRHMJ-UHFFFAOYSA-N
Pubchem ID :267139

Safety of [ 6134-54-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H318-H351-H411
Precautionary Statements:P273-P280-P305+P351+P338
Class:3
UN#:1993
Packing Group:

Calculated chemistry of [ 6134-54-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 46.77
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.

2.49
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

3.4
Log Po/w (WLOGP)?

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

2.94
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.

3.59
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

3.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.24

Water Solubility

Log S (ESOL):?

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

-3.65
Solubility 0.0443 mg/ml ; 0.000225 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.

-3.08
Solubility 0.164 mg/ml ; 0.000833 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

-4.08
Solubility 0.0163 mg/ml ; 0.0000826 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

Low
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

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

No
Log Kp (skin permeation)?

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

-5.09 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

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)

1.7

Application In Synthesis [ 6134-54-9 ]

* 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 [ 6134-54-9 ]

[ 6134-54-9 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 496-11-7 ]
  • [ 6134-53-8 ]
  • [ 6134-54-9 ]
YieldReaction ConditionsOperation in experiment
With benzyltrimethylazanium tribroman-2-uide; zinc dibromide; In acetic acid; at 20℃; for 4h; Reference Synthetic Example 51-[5-(2,3-Dihydro-1H-inden-5-yl)-4-hydroxythiophen-3-yl]ethanone(1) Synthesis of (2,3-dihydro-1H-inden-5-yl)boronic acid Synthesis was carried out by the following synthesis methods 3 and 4.Synthesis Method 35.91 g (0.05 mol) of 2,3-dihydro-1H-indene was stirred with 60 ml of acetic acid at room temperature, and to the resulting solution, 12.3 g (0.055 mol) of zinc (II) bromide was added and then 19.5 g (0.05 mol) of benzyltrimethylammonium tribromide was added. After the addition, the reaction solution was stirred at room temperature for 4 hours to complete the reaction. After completion of the reaction, the reaction solution was extracted by adding ethyl acetate and saturated aqueous sodium chloride. The ethyl acetate layer was neutralized and washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane) to isolate 5.11 g of an oil (yield: 51.9%). The oil turned out to be a mixture of about 70 to 80% of the 5-bromide and about 30 to 20% of the 4-bromide upon 1H-NMR analysis. 8.3 g (0.0421 mol) of 5-bromo-2,3-dihydro-1H-indene and 4-bromo-2,3-dihydro-1H-indene was stirred with 40 ml of dry tetrahydrofuran with cooling to -78 C., and 32.0 ml of 1.6 M n-butyllithium in n-hexane was added dropwise. After the dropwise addition, the reaction solution was stirred at -78 C. for 15 minutes, and 8.75 g (0.0842 mol) of trimethyl borate was added. After the dropwise addition, the reaction solution was stirred for 3 hours while the temperature was allowed to elevate to -20 C. Then, 50 ml of 1 M hydrochloric acid was added dropwise, and the reaction solution was stirred for 2 hours while the temperature was allowed to elevate to room temperature. The reaction solution was extracted by adding 300 ml of ethyl acetate and 250 ml of saturated aqueous sodium chloride. The ethyl acetate layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the ethyl acetate was evaporated under reduced pressure. The residual crystals were stirred with 20 ml of ethyl acetate and dispersed by adding 150 ml of n-hexane. The crystals were collected by filtration, washed with n-hexane and dried to obtain 2.5 g of the desired product (yield: 36.7%).
  • 2
  • [ 496-11-7 ]
  • [ 7726-95-6 ]
  • [ 64-19-7 ]
  • [ 6134-53-8 ]
  • [ 6134-54-9 ]
  • 3
  • [ 496-11-7 ]
  • C9H8Br2 [ No CAS ]
  • [ 6134-53-8 ]
  • [ 6134-54-9 ]
YieldReaction ConditionsOperation in experiment
With aluminum oxide; bromine; Bromine (6.40 g, 40.0 mmol) adsorbed on alumina (30 g, neutral, Brockmann grade 1) was added to indane (4.70 g, 40.0 mmol) also adsorbed on alumina (30 g, neutral, Brockmann grade 1). The mixture was stirred until the color of the bromine disappeared (tlc showed completion). The reaction mixture was filtered through silica gel (100 g eluting with CH2Cl2) and the filtrate was concentrated in vacuo to provide the crude bromoindane (7.40 g) as a brown oil. The crude material was purified by flash chromatography (200 g SiO2, hexanes) to give a mixture of 2 mono-brominated indanes and a dibrominated indane (5.95 g, 68%) as yellow oil.
Preparation of the Mixture of Boronic Acids. (According to Ranu, Synth. Comm. 1095 (1992) Bromine (6.40 g, 40.0 mmol) adsorbed on alumina (30 g, neutral, Brockmann grade 1) was added to indane (4.70 g, 40.0 mmol) also adsorbed on alumina (30 g, neutral, Brockmann grade 1). The mixture was stirred until the color of the bromine disappeared (tlc showed completion). The reaction mixture was filtered through silica gel (100 g eluting with CH2Cl2) and the filtrate was concentrated in vacuo to provide the crude bromoindane (7.40 g) as a brown oil. The crude material was purified by flash chromatography (200 g SiO2, hexanes) to give a mixture of 2 mono-brominated indanes and a dibrominated indane (5.95 g, 68%) as yellow oil.
  • 4
  • [ 6134-53-8 ]
  • [ 6134-54-9 ]
  • [ 196861-31-1 ]
  • [ 915411-11-9 ]
YieldReaction ConditionsOperation in experiment
An oven-dried flask was charged with the mixture of bromoindanes (340 mg, 1.73 mmol) and dry THF (2 mL) under argon. The solution was cooled to -78 C. and butyllithium (1.6 M in hexanes, 1.30 mL) was added drop-wise. The reaction mixture was stirred for 15 min at -78 C. and trimethyl borate (385 muL, 3.46 mmol) was added drop-wise. The reaction solution was left to warm to -20 C. over a period of 2.5 h and was then quenched with 1M aqueous HCl (2 mL). The mixture was left to warm to room temperature, was diluted with MTBE (20 mL) and the layers were separated. The organic layer was washed with H2O (5 mL) and brine 5 mL), dried (Na2SO4) and concentrated to give the crude boronic acid (232 mg). Flash chromatography (20 g SiO2, AcOEt/heptane 1:4?1:2) provided a mixture of 4- and 5-indane boronic acid (123 mg, 44%).
  • 5
  • [ 121-43-7 ]
  • [ 6134-53-8 ]
  • [ 6134-54-9 ]
  • [ 196861-31-1 ]
  • [ 915411-11-9 ]
YieldReaction ConditionsOperation in experiment
An oven-dried flask was charged with the mixture of bromoindanes (340 mg, 1.73 mmol) and dry THF (2 mL) under argon. The solution was cooled to -78 C. and butyllithium (1.6 M in hexanes, 1.30 mL) was added drop-wise. The reaction mixture was stirred for 15 min at -78 C. and trimethyl borate (385 muL, 3.46 mmol) was added drop-wise. The reaction solution was left to warm to -20 C. over a period of 2.5 h and was then quenched with 1M aqueous HCl (2 mL). The mixture was left to warm to room temperature, was diluted with MTBE (20 mL) and the layers were separated. The organic layer was washed with H2O (5 mL) and brine 5 mL), dried (Na2SO4) and concentrated to give the crude boronic acid (232 mg). Flash chromatography (20 g SiO2, AcOEt/heptane 1:4?1:2) provided a mixture of 4- and 5-indane boronic acid (123 mg, 44%).
 

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