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Chemical Structure| 6344-72-5 Chemical Structure| 6344-72-5

Structure of 6344-72-5

Chemical Structure| 6344-72-5

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Product Details of [ 6344-72-5 ]

CAS No. :6344-72-5
Formula : C9H8N2
M.W : 144.17
SMILES Code : CC1=CC=C2N=CC=NC2=C1
MDL No. :MFCD00041001
InChI Key :OSRARURJYPOUOV-UHFFFAOYSA-N
Pubchem ID :242567

Safety of [ 6344-72-5 ]

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

Computational Chemistry of [ 6344-72-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 10
Fraction Csp3 0.11
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 44.5
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.74
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

1.36
Log Po/w (WLOGP)?

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

1.94
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.

1.19
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

2.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.73

Water Solubility

Log S (ESOL):?

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

-2.26
Solubility 0.786 mg/ml ; 0.00545 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.

-1.5
Solubility 4.52 mg/ml ; 0.0313 mol/l
Class?

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

Very 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

-3.69
Solubility 0.0294 mg/ml ; 0.000204 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.

-6.21 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)

1.26

Application In Synthesis of [ 6344-72-5 ]

* 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 [ 6344-72-5 ]

[ 6344-72-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [2-(Phenyl-hydrazono)-eth-(E)-ylidene]-m-tolyl-amine [ No CAS ]
  • [ 6344-72-5 ]
  • [ 13708-12-8 ]
  • 2
  • [ 6344-72-5 ]
  • [ 53967-21-8 ]
YieldReaction ConditionsOperation in experiment
35% With N-Bromosuccinimide;dibenzoyl peroxide; In tetrachloromethane; for 48h;Reflux; A mixture of 6-methylquinoxaline (2.0 g, 13.9 mmol), N-bromosuccinimide (3.0 g, 16.9 mmol), and benzoyl peroxide (411 mg, 1.7 mmol) in anhydrous carbon tetrachloride (50 mL) was stirred at reflux for 2 days. Dichloromethane (50 mL) was added after cooling to room temperature. The mixture was extracted with 1 N NaOH (1 x 100 mL) and brine (1 x 100 mL). The organic extract was recovered, dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude product was purified by flash chromatography (0-30% EtOAc/hexanes), affording 6- (bromomethyl)quinoxaline (1.10 g, 35% yield).
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 18h;Inert atmosphere; Reflux; Intermediate 17: 6-(bromomethyl)quinoxaline A mixture of 6-methylquinoxaline (300 mg), NBS (370 mg) and benzoyl peroxide (5.04 mg) in carbon tetrachloride (8 ml.) was heated at reflux under an atmosphere of argon for 18 hr. The reaction mixture was cooled to RT, filtered and concentrated under reduced pressure to give a brown oil. The crude product was purified by column chromatography (Biotage SP4, 40+M column, 20-100% EtOAc / isohexane. The fractions containing product were combined and concentrated under reduced pressure to give the title compound (243 mg) as a white solid, m/z [M+H]+: 223.1 / 225.0. Retention time 0.80 min (LC/MS method 3).
With N-Bromosuccinimide; dibenzoyl peroxide; Example 292 Synthesis of 6-(bromomethyl)quinoxaline. To a solution of 6-methylquinoxaline (5 g, 34.7 mmol) in DCE (100 mL) was added NBS (7.12 g, 40 mmol) and benzoyl peroxide (840 mg, 3.47 mmol). The reaction mixture was stirred at 85 C. for 16 h under nitrogen. H2O (100 mL) was added, and the mixture was extracted with DCM (150 mL*3). The combine organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product which was purified by silica gel chromatography (PE/EtOAc=1/1) to give 6-(bromomethyl)quinoxaline as a yellow solid. (5.5 g, 71%). ESI-MS [M+H]+: 224.1.
  • 3
  • [ 6344-72-5 ]
  • C9H6Br2N2 [ No CAS ]
  • [ 53967-21-8 ]
YieldReaction ConditionsOperation in experiment
23%; 77% With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; for 5h;Heating / reflux; Example 9 6-Bromomethylquinoxaline: A mixture of 6-methylquinoxaline (1.5 g, 10.4 mmol), N-bromosuccinimide (2.2 g, 12.5 mmol) and benzoylperoxide (0.30 g, 1.25 mmol) in benzene (35 mL) was stirred rapidly and heated to reflux for 5 h. Upon cooling the mixture was diluted with ethyl acetate (25 mL), washed with 1N sodium hydroxide solution (50 mL) and saturated sodium chloride solution (50 mL). The organic layer was dried (MgSO4) and evaporated to a crystalline solid (2.5 g, 77% desired product, 23% alpha,alpha-dibrominated product as determined by 1H NMR). The mixture was used in subsequent reactions.
23%; 77% With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; for 5h;Heating / reflux; 6-Bromomethyl-quinoxaline: A mixture of 6-methylquinoxaline (1.5 g, 10.4 mmol), N-bromosuccinimide (2.2 g, 12.5 mmol) and benzoylperoxide (0.30 g, 1.25 mmol) in benzene (35 mL) was stirred rapidly and heated to reflux for 5 h. Upon cooling, the mixture was diluted with ethyl acetate (25 mL), washed with IN sodium hydroxide solution (50 mL) and saturated sodium chloride solution (50 mL). The organic layer was dried (MgSO4) and evaporated to a crystalline solid (2.5 g, 77% desired product, 23% alpha,alpha-dibrominated product as determined by 1H NMR). The mixture was used in subsequent reactions.
36% With N-Bromosuccinimide;2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 2h;Heating / reflux; 6-Bromomethylquinoxaline (1) (De Selms, R. C.; Greaves, R. J., Scheigh, W. R. J. Het. Chem. 1974, 11, 595); Bromomethylquinoxaline is unstable and decomposes when stored for long time. It should be used up within a day or two of its preparation. To a clear solution of 6-methylquinoxaline (60 g, 0.416 mol) in 550 mL of CCl4 was added in one portion solid NBS (Aldrich, 81.5 g, 0.458 mol, 1.1 eq) and AlBN (Aldrich, 1.6 g, 9.7 mmol, 2.3 mol %). The resulting mixture was heated at reflux for 2 hr and cooled to rt. The precipitate of succinimide was removed by filtration. The filtrate was evaporated on rotary evaporator until solid begins to crystallize out of the solution. Remaining mixture was left at rt for 2 hr, then the crystallized product was filtered off, washed with small amount of hexanes-CCl4 mixture (ca. 20:1) and dried in vacuum. The isolated solid contained just traces of the di-bromo side-product and was used in the following step without further purification. Yield 33.3 g (36%) as colorless crystals.
  • 4
  • [ 6344-72-5 ]
  • [ 53967-21-8 ]
  • [ 488834-75-9 ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide; dibenzoyl peroxide; In 1,2-dichloro-ethane; Example 3 Preparation of a Solid Sample of 6-bromomethyl-quinoxaline In a 100 ml flask, 6-methyl-quinoxaline (2.5 g, 17.4 mmol) was dissolved together with N-bromosuccinimide (4.63 g, 19 mmol) and benzoyl peroxide (0.3 g, 1.24 mmol) in 70 g of 1,2-dichloroethane. The solution was refluxed for 150 minutes and analyzed. The concentrations of the reactants and some of their molar ratios are shown below: The solution was cooled in the freezer overnight and the solid residue was separated by filtration. The solid was washed with pentane and the washings were combined with the liquid fraction. The clear reddish solution was then vacuum dried to give an orange solid that was used in the preparation of 6-hydroxymethyl-quinoxaline.
 

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