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Chemical Structure| 16932-45-9

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Product Details of [ 16932-45-9 ]

CAS No. :16932-45-9
Formula : C8H9BrO2
M.W : 217.06
SMILES Code : COC1=CC=CC(OC)=C1Br
MDL No. :MFCD07780177
Boiling Point : No data available
InChI Key :VHVYSMMZHORFKU-UHFFFAOYSA-N
Pubchem ID :612296

Safety of [ 16932-45-9 ]

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

Computational Chemistry of [ 16932-45-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.13
TPSA ?

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

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.4
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

2.2
Log Po/w (WLOGP)?

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

2.47
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.

2.22
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

2.49
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.35

Water Solubility

Log S (ESOL):?

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

-2.84
Solubility 0.311 mg/ml ; 0.00143 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.

-2.22
Solubility 1.3 mg/ml ; 0.006 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

-3.51
Solubility 0.0668 mg/ml ; 0.000308 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.

-6.06 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

0.0
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)

1.51

Application In Synthesis of [ 16932-45-9 ]

* 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 [ 16932-45-9 ]

[ 16932-45-9 ] Synthesis Path-Downstream   1~35

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  • C22H21(2)HO4 [ No CAS ]
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  • [ 122452-59-9 ]
YieldReaction ConditionsOperation in experiment
With titanium tetrachloride; In dichloromethane; at -40 - 20℃; for 16h; 2-Bromo-1,3-dimethoxybenzene (2.22 g, 10.2 mmol) dissolved into anhydrous dichloromethane (25 mL), chilled near -40 C. and treated over a few minutes with 1 M TiCl4 in dichloromethane (15.3 mL, 15.3 mmol) followed several minutes later with dichloro(methoxy)methane (1.0 mL, 11.1 mmol). The reaction mixture and Dewer flask were covered with insulation, allowed to warm slowly to ambient temperature for 16 hours and then poured over ice. The product was extracted into dichloromethane and the combined extracts were dried (Na2SO4), concentrated and chromatographed on silica (20 to 40% methyl tert-butyl ether/heptane) to give the title compound. 1H NMR (501 MHz, CDCl3) delta ppm 10.23 (d, J=0.8 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 6.82 (dd, J=8.8, 0.8 Hz, 1H), 3.99 (s, 3H), 3.99 (s, 3H)+ MS (DCI) m/z 245/247 (M+H)+.
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  • 22
  • [ 151-10-0 ]
  • [ 16932-45-9 ]
YieldReaction ConditionsOperation in experiment
52% EXAMPLES Production Example (A) Synthesis of Intermediate (A) [Show Image] (A-1) Synthesis of 1-bromo-2,6-dimethoxybenzene In the atmosphere of argon, 19.3g of 1,3-dimethoxybenzene and 500 mL of anhydrous diethyl ether were placed in a flask. 105 mL (1.6M) of a hexane solution of n-butyllithium was added, and the resulting reaction solution was stirred with heating for 4 hours. After cooling to room temperature while stirring, the reaction solution was cooled to -50C, followed by dropwise addition of 25g of bromine. Then, while heating the reaction solution to room temperature, stirring was conducted for 2 hours. Then, 300 mL of an aqueous 10% sodium thiosulfate solution was added, and the resulting mixture was stirred for 1 hour. The reaction solution was extracted with ether, and an aqueous phase was removed, and then, an organic phase was washed with saturated saline. The organic phase was dried with magnesium sulfate and concentrated. Residues were purified by means of silica gel column chromatography. The resulting crystals were washed with hexane, whereby 17.9g (yield: 52%) of white crystals of 1-bromo-2,6-dimethoxybenzene were obtained.
52% Under an argon atmosphere 1,3-dimethoxy benzene (19.3g), was charged with anhydrous diethyl ether (500mL) to the flask, added 1.6M n-butyl lithium in hexane solution (105mL), the reaction solution was stirred for 4 hours under heating. After cooling to room temperature with continuous stirring, cooled to -50 C., was added dropwise bromine (25 g). The reaction solution was stirred for 2 hours while warming to room temperature. 10% aqueous solution of sodium thiosulfate (300mL) added, and the mixture was stirred for 1 hour. The reaction solution was extracted with ether, after removing the aqueous layer, the organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate, concentrated, and the residue was purified by silica gel chromatography. The obtained crystals were washed with hexane to obtain Intermediate 14 (17.9g). The yield was 52%.
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  • [ 159506-56-6 ]
  • 27
  • [ 16932-45-9 ]
  • 2-carboxy-3,4,5,6-tetrachlorobenzendiazonium chloride [ No CAS ]
  • [ 55416-15-4 ]
  • 30
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  • [ 4688-76-0 ]
  • [ 223268-67-5 ]
  • 31
  • [ 16932-45-9 ]
  • Benzo[1,4]dioxine-2-carboxylic acid diisopropylamide [ No CAS ]
  • 3-(2-Methoxy-phenyl)-benzo[1,4]dioxine-2-carboxylic acid diisopropylamide [ No CAS ]
  • 32
  • [ 16932-45-9 ]
  • 3-Tributylstannanyl-benzo[1,4]dioxine-2-carboxylic acid diisopropylamide [ No CAS ]
  • 3-(2,6-Dimethoxy-phenyl)-benzo[1,4]dioxine-2-carboxylic acid diisopropylamide [ No CAS ]
  • 35
  • [ 106-93-4 ]
  • 2,6-dimethoxy-phenyl lithium [ No CAS ]
  • [ 16932-45-9 ]
 

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Technical Information

Categories

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[ 16932-45-9 ]

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