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Structure of 95970-08-4

Chemical Structure| 95970-08-4

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Product Details of [ 95970-08-4 ]

CAS No. :95970-08-4
Formula : C7H6Br2O
M.W : 265.93
SMILES Code : COC1=CC(Br)=CC=C1Br
MDL No. :MFCD07780698
InChI Key :YJGNTPRGNRICPY-UHFFFAOYSA-N
Pubchem ID :13399557

Safety of [ 95970-08-4 ]

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

Computational Chemistry of [ 95970-08-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 48.33
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.

2.59
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

2.56
Log Po/w (WLOGP)?

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

3.22
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.

3.3
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

3.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.97

Water Solubility

Log S (ESOL):?

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

-3.48
Solubility 0.0881 mg/ml ; 0.000331 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.

-2.4
Solubility 1.05 mg/ml ; 0.00397 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

-4.23
Solubility 0.0156 mg/ml ; 0.0000587 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

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

Yes
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.

-6.1 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<0.0
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)

1.62

Application In Synthesis of [ 95970-08-4 ]

* 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.

  • Upstream synthesis route of [ 95970-08-4 ]

[ 95970-08-4 ] Synthesis Path-Upstream   1~11

  • 1
  • [ 19056-40-7 ]
  • [ 95970-08-4 ]
YieldReaction ConditionsOperation in experiment
81%
Stage #1: With sulfuric acid; sodium nitrite In water at 12℃;
Stage #2: With hydrogen bromide; copper(I) bromide In water at 40 - 65℃;
adding 1020 g of 2-bromo-5-aminoanisole to the reaction vessel,Add about 30percent sulfuric acid 8380 g and stir.Then, a solution of 455 g of sodium nitrite and 1000 g of water was added dropwise, and the process temperature was controlled at about 12 °C.After the addition is completed, the mixture is stirred for a while to prepare a diazonium salt for use. Add 520 g of cuprous bromide and HBr 1350 g to another reaction flask.The above diazonium salt is added under stirring, and the temperature rises when decomposed, and the controlled temperature is 40 to 65 °C.After the addition, continue to stir, keep the reaction for a period of time, stir, cool, filter,The brown solid 2,5-dibromoanisole was obtained in an amount of 1086 g, and the content was more than 97percent, and the yield was 81percent.
References: [1] Patent: CN109320403, 2019, A, . Location in patent: Paragraph 0011; 0013; 0014; 0016; 0018; 0019.
  • 2
  • [ 67-56-1 ]
  • [ 1435-52-5 ]
  • [ 95970-08-4 ]
YieldReaction ConditionsOperation in experiment
84% With potassium <i>tert</i>-butylate In tetrahydrofuran; hexane at 20 - 70℃; Preparation 111; 1 ,4-Dibromo-2-methoxy-benzene; Add dropwise potassium tert-butoxide (118.2 ml, 118.2 mmol, 1 M in hexane) to a solution of l,4-dibromo-2-fluorobenzene (25.0 g, 98.5 mmol) in THF (492 mL) and MeOH (40 mL, 984.7 mmol) at RT. Heat the mixture at 70 0C overnight. Quench the mixture with water (50 mL), dilute with Et2O (400 mL), wash once with saturated NH4Cl (300 mL) and back extract the aqueous with Et2O (200 mL). Dry the combined organic phase over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatograph, eluting with 5-10percent ethylacetate/hexane to give 22.0 g (84percent) of the title compound. GC m/z (79Br81Br) 266 [M]+.
References: [1] Patent: WO2007/146758, 2007, A2, . Location in patent: Page/Page column 76.
  • 3
  • [ 28165-52-8 ]
  • [ 77-78-1 ]
  • [ 95970-08-4 ]
References: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 9, p. 2450 - 2454[2] Angew. Chem., 2018, vol. 130, # 9, p. 2475 - 2479,5.
  • 4
  • [ 72135-36-5 ]
  • [ 95970-08-4 ]
References: [1] Chemical Science, 2018, vol. 9, # 15, p. 3860 - 3865.
  • 5
  • [ 28165-52-8 ]
  • [ 74-88-4 ]
  • [ 95970-08-4 ]
References: [1] Chemical Communications, 2011, vol. 47, # 29, p. 8259 - 8261.
  • 6
  • [ 129319-11-5 ]
  • [ 95970-08-4 ]
References: [1] Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, p. 2357 - 2366[2] Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 12, p. 2588 - 2599.
  • 7
  • [ 51-66-1 ]
  • [ 95970-08-4 ]
References: [1] Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, p. 2357 - 2366[2] Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 12, p. 2588 - 2599.
  • 8
  • [ 77337-82-7 ]
  • [ 95970-08-4 ]
References: [1] Patent: CN109320403, 2019, A, .
  • 9
  • [ 97-52-9 ]
  • [ 95970-08-4 ]
References: [1] Patent: CN109320403, 2019, A, .
  • 10
  • [ 95970-09-5 ]
  • [ 95970-08-4 ]
References: [1] Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, p. 2357 - 2366[2] Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 12, p. 2588 - 2599.
  • 11
  • [ 615-54-3 ]
  • [ 124-41-4 ]
  • [ 21702-84-1 ]
  • [ 62415-74-1 ]
  • [ 95970-08-4 ]
References: [1] Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, # 3, p. 516 - 522[2] Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 3, p. 577 - 583.
 

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