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Chemical Structure| 26670-89-3 Chemical Structure| 26670-89-3
Chemical Structure| 26670-89-3

2-Bromo-4-iodo-1-methylbenzene

CAS No.: 26670-89-3

4.5 *For Research Use Only !

Cat. No.: A212182 Purity: 98%

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Product Details of [ 26670-89-3 ]

CAS No. :26670-89-3
Formula : C7H6BrI
M.W : 296.93
SMILES Code : CC1=C(Br)C=C(I)C=C1
MDL No. :MFCD07779014
InChI Key :ANRAKTDEUFLKDO-UHFFFAOYSA-N
Pubchem ID :21560038

Safety of [ 26670-89-3 ]

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

Computational Chemistry of [ 26670-89-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 51.83
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.

2.53
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

3.63
Log Po/w (WLOGP)?

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

3.36
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.

4.25
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

3.95
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.54

Water Solubility

Log S (ESOL):?

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

-4.46
Solubility 0.0103 mg/ml ; 0.0000346 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.32
Solubility 0.143 mg/ml ; 0.000481 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

-4.58
Solubility 0.00786 mg/ml ; 0.0000265 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

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.

-5.53 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

1.0
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)

1.88

Application In Synthesis of [ 26670-89-3 ]

* 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 [ 26670-89-3 ]

[ 26670-89-3 ] Synthesis Path-Upstream   1~4

  • 1
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  • [ 26670-89-3 ]
YieldReaction ConditionsOperation in experiment
92.2%
Stage #1: With hydrogenchloride In water at 90℃; for 1 h;
Stage #2: With sodium nitrite In water at -10 - 5℃; for 0.5 h;
Stage #3: With potassium iodide In water at 10 - 40℃; for 4 h;
450 mL of water, 50.0 g (0.268 mol) of 2-bromo-p-toluidine,100 mL (1.102 mol) of concentrated hydrochloric acid was added and heated to 90 ° C. with stirring.Subsequently, the mixture was stirred at the same temperature for 1 hour, then cooled to room temperature, and further cooled to -10 ° C. with an ice water bath. Next, an aqueous solution prepared by dissolving 22.3 g (0.323 mol) of sodium nitrite in 70 mL of water was added dropwise at a temperature not exceeding 5 ° C., followed by stirring at 5 ° C. or lower for 30 minutes, filtration with an aid, diazonium An aqueous solution of salt was obtained.Next, 67.0 g (0.403 mol) of potassium iodide (Wako Pure Chemical Industries, Ltd.) and 230 mL of water were added to a 1 L four-necked round bottom flask equipped with a stirrer, Erlin condenser, 1 L dropping funnel and thermometer The mixture was placed in a water bath and stirred at 10 ° C. Next, after the aqueous solution of the diazonium salt was dropped, the water bath was removed to return to room temperature, the temperature was further increased to 40 ° C., and the mixture was stirred for 4 hours. The obtained reaction solution was returned to room temperature again, 300 mL of DCM was added and the mixture was transferred to a 2 L separatory funnel, then the aqueous layer was separated and extracted with 250 mL of DCM. Next, the DCM layers were combined, washed with 250 mL of 20percent sodium thiosulfate aqueous solution, 250 mL of saturated aqueous multilayer water, three times with 250 mL of water, dried with magnesium sulfate, then removed by suction filtration of magnesium sulfate, The solvent was distilled off under reduced pressure. Subsequently, the resulting crude oil was purified by silica gel column chromatography using n-heptane as a developing solvent to obtain 73.5 g (yield 92.2percent) of the desired iodide.
49%
Stage #1: With hydrogenchloride; sodium nitrite In water at -8 - 0℃; for 0.75 h; Inert atmosphere
Stage #2: With potassium iodide In water at 0℃; for 3 h; Inert atmosphere
(2-1) Synthesis of 2-Bromo-4-Iodotoluene (0143) A mixture of 3-bromo-4-methylaniline (18.6 g) and 6 M hydrochloric acid (80 mL) was cooled to −5° C. in an argon atmosphere. After the dropwise addition of an aqueous solution (15 mL) of sodium nitrite (7.35 g) while maintaining the mixture at 0° C. or less, the resulting mixture was stirred at −8° C. for 45 minutes. Potassium iodide (33.2 g) was added to the mixture over 3 hours while maintaining the mixture at 00° C. or less. The resulting reaction mixture was returned to room temperature. After the addition of a 10percent sodium hydrogen sulfite aqueous solution (50 mL), the mixture was extracted with diethyl ether. The organic layer was washed with a 10percent sodium hydrogen sulfite aqueous solution, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 2-bromo-4-iodotoluene (14.5 g). The yield was 49percent.
0.053 mol,53% With potassium iodide; sodium nitrite In hydrogenchloride; hexane; water Step A:
2-Bromo-4-iodotoluene
A well stirred solution of 18.6 g (0.10 mol) of 3-bromo-p-toluidine in 80 mL of 6N HCl at 0° C. was treated with a solution of 7.35 g (0.11 mol) of sodium nitrite in 15 mL of water at a rate that maintained the temperature <10° C.
The mixture was stirred for 45 minutes then cautiously treated with 33.2 g (0.20 mol) of potassium iodide at 0° C.
The mixture was treated with 300 mL of ether and washed (3*) with saturated aqueous sodium bisulfite.
The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under vacuum.
The residue was redissolved in 50 mL of hexane, filtered through 30 g of silica and concentrated under vacuum to afford 15.6 g (0.053 mol,53percent) of the product which was determined to be 65percent pure by 1 H NMR. 1 H NMR (200 MHz,CDCl3):
2.33 (s,3H), 6.97 (d,8 Hz,1H), 7.51 (dd;2,8 Hz,1H), 7.86 (d,2 Hz,1H).
References: [1] Patent: JP2018/90561, 2018, A, . Location in patent: Paragraph 0087.
[2] Photochemical and Photobiological Sciences, 2018, vol. 17, # 3, p. 290 - 301.
[3] Patent: US2017/183291, 2017, A1, . Location in patent: Paragraph 0142; 0143.
[4] Patent: US5206235, 1993, A, .
  • 2
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  • [ 26670-89-3 ]
References: [1] Journal of the Indian Chemical Society, 1936, vol. 13, p. 187.
  • 3
  • [ 624-31-7 ]
  • [ 26670-89-3 ]
References: [1] Chemische Berichte, 1896, vol. 29, p. 1410.
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  • [ 26670-89-3 ]
References: [1] Chemische Berichte, 1896, vol. 29, p. 1410.
 

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