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Chemical Structure| 29578-83-4 Chemical Structure| 29578-83-4

Structure of 29578-83-4

Chemical Structure| 29578-83-4

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Product Details of [ 29578-83-4 ]

CAS No. :29578-83-4
Formula : C8H9BrO
M.W : 201.06
SMILES Code : CC1=CC(OC)=CC(Br)=C1
MDL No. :MFCD08061916
InChI Key :AOEVRCZZWJWKPG-UHFFFAOYSA-N
Pubchem ID :10679554

Safety of [ 29578-83-4 ]

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

Computational Chemistry of [ 29578-83-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 45.6
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.54
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

2.95
Log Po/w (WLOGP)?

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

2.77
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.

2.88
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

2.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.82

Water Solubility

Log S (ESOL):?

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

-3.32
Solubility 0.0956 mg/ml ; 0.000475 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.

-2.81
Solubility 0.314 mg/ml ; 0.00156 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

-3.77
Solubility 0.0342 mg/ml ; 0.00017 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.

-5.43 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

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)

1.42

Application In Synthesis of [ 29578-83-4 ]

* 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 [ 29578-83-4 ]

[ 29578-83-4 ] Synthesis Path-Downstream   1~6

  • 3
  • [ 29578-83-4 ]
  • [ 262450-65-7 ]
  • 4
  • [ 74204-00-5 ]
  • [ 29578-83-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; dimethyl sulfate; In water; EXAMPLE 9 A mixture of <strong>[74204-00-5]5-bromo-3-hydroxytoluene</strong> (93 g, 0.5 m) and sodium hydroxide (21 g, 0.5 m) in water (200 ml) is stirred at 10°, treated with dimethyl sulfate (63 g, 0.5 m) over 1 hour, refluxed for 2 hours and cooled. The mixture is diluted with water and extracted with ether. The ether extract is washed, dried with sodium sulfate and concentrated in vacuo to give 5-bromo-3-methoxytoluene.
  • 5
  • [ 74137-36-3 ]
  • [ 74-88-4 ]
  • [ 29578-83-4 ]
YieldReaction ConditionsOperation in experiment
2 mmol <strong>[74137-36-3]3,5-dibromoanisole</strong> were dissolved in 10 ml THF and cooled to -78°C. 2.4 mmol of n- BuLi were added dropwise and stirring was continued for 15 min. 3 mmol of methyl iodide were added and the mixture was allowed to slowly warm to ca. -200C over a period of ca. 2 h. IM HCl and dichloromethane were added and the phases were separated. 1.65 mmol of crude 3-bromo-5- methylanisole were taken to the next step without further purification.
  • 6
  • [ 74204-00-5 ]
  • [ 74-88-4 ]
  • [ 29578-83-4 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate; In acetone; at 40℃; for 16.0h; To a mixture of <strong>[74204-00-5]3-bromo-5-methyl-phenol</strong> (185 g; 0.940 mol) and K2CO3 (437 g, 3.17 mol) in acetone (2 L) is added MeI (424 g, 2.99 mol). The mixture is stirred at 40° C. for 16 h. The mixture is cooled to ambient temperature, filtered, and concentrated under reduced pressure. After filtration, the mixture is purified by flash silica gel chromatography to afford 1-Bromo-3-methoxy-5-methyl-benzene, D-4-1 (189 g, quant. yield) as a light yellow oil.
85.8% With potassium carbonate; In acetonitrile; for 3.0h;Reflux; C. Preparation of 3-methyl-5-methoxybromobenzene In a three-necked flask, 3-methyl 5-bromophenol (10.0 g, 53.5 mmol), potassium carbonate (22.2 g, 160.4 mol) andIodomethane (7.6 g, 53.5 mol) was dissolved in acetone (50 mL) and refluxed for 3 h. After the reaction is complete, add 30 mL of water, methylene chloride(50mL × 3) extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated under reduced pressure to give 3-methyl-5-methoxybromobenzene white.Crystals 9.2 g, yield 85.8percent
52% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24.0h; [0297] To the mixture of compound 29-1 (300 g, 1.6 mol) and K2CO3 (665 g, 4.8 mol) in DMF (2000 mL) was added MeI (250 g, 1.8 mol) dropwised at room temperature. The mixture was stirred overnight. TLC showed the reaction is completed. The reaction was quenched by H2O and extracted with EtOAc. The organic layer was dried, filtered, evaporated under reduced pressure to give the crude product which was purified by chromatography on silica gel to give compound 29-2 (165 g, 52percent yield).
 

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