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Chemical Structure| 4028-63-1 Chemical Structure| 4028-63-1
Chemical Structure| 4028-63-1

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2,4,6-Trimethyliodobenzene

CAS No.: 4028-63-1

4.5 *For Research Use Only !

Cat. No.: A175743 Purity: 98% (stabilized with Copper chip)

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Product Details of [ 4028-63-1 ]

CAS No. :4028-63-1
Formula : C9H11I
M.W : 246.09
SMILES Code : CC1=C(I)C(C)=CC(C)=C1
MDL No. :MFCD00013707
InChI Key :GTPNXFKONRIHRW-UHFFFAOYSA-N
Pubchem ID :77647

Safety of [ 4028-63-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P305+P351+P338

Calculated chemistry of [ 4028-63-1 ] 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 54.06
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.

2.62
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

4.39
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.

4.12
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

4.19
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.71

Water Solubility

Log S (ESOL):?

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

-4.58
Solubility 0.00654 mg/ml ; 0.0000266 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.

-4.11
Solubility 0.0192 mg/ml ; 0.0000782 mol/l
Class?

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

Moderately 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

-4.51
Solubility 0.00752 mg/ml ; 0.0000305 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.

-4.68 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

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<2.0
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)

1.76

Application In Synthesis [ 4028-63-1 ]

* 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 [ 4028-63-1 ]

[ 4028-63-1 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 4028-63-1 ]
  • [ 1066-54-2 ]
  • [ 769-26-6 ]
  • [ 5806-58-6 ]
YieldReaction ConditionsOperation in experiment
11%; 74% General procedure: 4-Iodoanisole (1mmol), TMSA (1.1mmol) and K2CO3 (2mmol) were added to a freshly prepared solution of PdNPs (5mL) in a 25mL round bottomed flask fitted with stopper. Then, the reaction mixture was stirred at 40C. The reaction progress was monitored by TLC, until complete consumption of aryl iodide. To the reaction mixture containing in situ formed 4-ethynylanisole the next batch of aryliodide (1mmol) was added and the reaction mixture was further allowed to stir until complete consumption of the arylacetylene. In this manner the targeted unsymmetrical diarylacetylene was formed. The detailed procedure is provided in the Supp. Info. Detailed procedure for synthesis of symmetrical diarylacetylenes is also mentioned in SI.
  • 2
  • [ 4028-63-1 ]
  • [ 1066-54-2 ]
  • [ 769-26-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In methanol; acetonitrile; at 45℃; General procedure: 4-Iodoanisole (1mmol), TMSA (1.1mmol) and K2CO3 (2mmol) were added to a freshly prepared solution of PdNPs (5mL) in a 25mL round bottomed flask fitted with stopper. Then, the reaction mixture was stirred at 40C. The reaction progress was monitored by TLC, until complete consumption of aryl iodide. To the reaction mixture containing in situ formed 4-ethynylanisole the next batch of aryliodide (1mmol) was added and the reaction mixture was further allowed to stir until complete consumption of the arylacetylene. In this manner the targeted unsymmetrical diarylacetylene was formed. The detailed procedure is provided in the Supp. Info. Detailed procedure for synthesis of symmetrical diarylacetylenes is also mentioned in SI.
  • 3
  • [ 1006-68-4 ]
  • [ 4028-63-1 ]
  • 5-phenyl-2-(2,4,6-trimethylphenylselanyl)-1,3-oxazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With selenium; caesium carbonate; copper dichloride; In N,N-dimethyl-formamide; at 20 - 140℃; for 24h;Inert atmosphere; In room temperature,2,4,6-trimethyliodobenzene (1.2 mmol, 3 equiv), elemental selenium (1.2 mmol, 3 equiv), <strong>[1006-68-4]5-phenyl-1,3-oxazole</strong> (0.4 mmol, 1 equiv), Copper chloride (0.04 mmol), cesium carbonate (1.2 mmol, 3 equiv) was added to the reaction tube, then filled with nitrogen, and replaced three times. Under a nitrogen reaction, 2 mL of N,N-dimethylformamide was added. The solvent was stirred at a reaction temperature of 140 C for 24 h. After monitoring the reaction by thin layer chromatography, the reaction mixture was cooled, then diluted with ethyl acetate, and the diluted solution was transferred to a separating funnel, and extracted with saturated brine to separate the aqueous and organic phases, and then acetic acid. The aqueous phase was extracted three times with ethyl acetate. The organic phase was combined, 5 g anhydrous sodium sulfate was added, and the mixture was allowed to stand for 30 min, and the filter cake was washed three times with 5 mL of ethyl acetate each time, then the solvent was spun off, and the product was isolated by column chromatography. Detachment: petroleum ether: ether = 98:2), the product was a yellow solid.The melting point was 65-66 C, the yield was 51%, and the weight of the product was 70 mg.
  • 4
  • [ 4028-63-1 ]
  • [ 118994-89-1 ]
  • 2-(2,4,6-trimethylphenylseleno)-1,3-oxazole-5-carboxylic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With selenium; potassium phosphate; copper(l) chloride; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; In room temperature, 2,4,6-trimethyliodobenzene (12 mmol, 3 equiv), elemental selenium (12 mmol, 3 equiv), ethyl 1,3-oxazol-5-carboxylate (4 mmol, 1 equiv), copper chloride (0.4 mmol) and potassium phosphate (12 mmol, 3 equiv) were added to the reaction tube, then filled with nitrogen, and replaced three times. In a nitrogen reaction environment, then 20 mL of N,N-dimethylformamide reaction solvent was added. Stir at a reaction temperature of 140 C for 24 h. After monitoring the reaction by thin layer chromatography, the reaction mixture was cooled. Then, ethyl acetate was added for dilution, and the diluted solution was transferred to a separatory funnel and extracted with saturated brine. The aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, 25 g of anhydrous sodium sulfate was added, and the mixture was stood still for 30 min. Wash the filter cake 3 times with 50 mL of ethyl acetate each time. Then spin off the solvent, the product was isolated by column chromatography (eluent: petroleum ether: diethyl ether = 98:2), yield 77%, product weight: 1.044 g.
 

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