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Chemical Structure| 5462-30-6

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Product Details of [ 5462-30-6 ]

CAS No. :5462-30-6
Formula : C8H6Cl2N2O3
M.W : 249.05
SMILES Code : CC(NC1=CC(Cl)=C(Cl)C=C1[N+]([O-])=O)=O
MDL No. :MFCD00024301
InChI Key :ZEGRPTYRAGSSBH-UHFFFAOYSA-N
Pubchem ID :226498

Safety of [ 5462-30-6 ]

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

Computational Chemistry of [ 5462-30-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 59.6
TPSA ?

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

74.92 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.75
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

2.41
Log Po/w (WLOGP)?

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

2.67
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.

1.59
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

0.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.8

Water Solubility

Log S (ESOL):?

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

-3.0
Solubility 0.249 mg/ml ; 0.000999 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.

-3.63
Solubility 0.059 mg/ml ; 0.000237 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

-3.4
Solubility 0.0985 mg/ml ; 0.000395 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

Yes
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.

-6.11 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

0.0
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

2.0 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)

2.22

Application In Synthesis of [ 5462-30-6 ]

* 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 [ 5462-30-6 ]

[ 5462-30-6 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 2150-93-8 ]
  • [ 5462-30-6 ]
YieldReaction ConditionsOperation in experiment
95.23% at 3 - 13℃; for 6.5 h; 3,4-Dichloroacetanilide (II) (150 g, 0.74 moles) was slowly added to a reactor containing sulfuric acid (270 g, 99percent, 2.7 moles) at 13 °C, followed by stirring for 0.5 hours and then cooling to 8 °C. To this, oleum (422 g, 31.1percent, 4.61 moles) was added slowly, to obtain a mixture. The mixture comprised resultant sulfuric acid having strength of 104percent. The molar ratio of 3,4-dichloroacetanilide (II) and the resultant sulfuric acid in the mixture was 1: 10. The mixture was further cooled to 3 °C, and nitric acid (51 g, 98percent, 0.79 moles) was slowly added to the mixture over 5 hours. The resultant mixture was further stirred and the progress of the reaction was monitored by thin layer chromatography (TLC). 3,4-Dichloroacetanilide was completely consumed within 1 hour and a product mixture was obtained. The product mixture was carefully poured over 1650 g ice in 200 ml water while maintaining the temperature below 15 °C, followed by stirring for 15 min to obtain a dispersion. The dispersion was filtered to obtain a residue comprising 2-nitro-4,5-dichloroacetanilide (I). The residue was washed with water till it was free of residual acid, and the washed residue was dried to obtain 2-nitro-4,5-dichloroacetanilide (I) (174 g, yield = 95.23percent, HPLC purity = 97.83percent). (0069) HPLC analysis of the product showed the presence of 1.46percent III.
References: [1] Patent: WO2018/91978, 2018, A1, . Location in patent: Page/Page column 7-8.
[2] Journal of Medicinal Chemistry, 1995, vol. 38, # 10, p. 1786 - 1792.
  • 2
  • [ 2150-93-8 ]
  • [ 5462-30-6 ]
YieldReaction ConditionsOperation in experiment
92% at 3 - 13℃; for 6.5 h; Experiment 3: 3,4-Dichloroacetanilide (II) (150 g, 0.735 moles), sulfuric acid (156.0 g, 99percent w/w, 1.576 moles), oleum (260.5 g, 31.1percent w/w, 2.844 moles), and nitric acid (51 g, 98percent w/w, 0.79 moles) were used. The mixture comprised resultant sulfuric acid having strength of 104percent. The molar ratio of 3,4-Dichloroacetanilide (II) to the resultant sulfuric acid in the mixture was 1:6. The reaction conditions, and product yield and purity are summarized in Table 1. (0074) 177 g of 2-nitro-4,5-dichloroacetanilide (I) was obtained (yield = 92percent and HPLC purity of 92percent). HPLC analysis of product showed the presence of 6percent of III. 3,4-Dichloroacetanilide (II) (150 g, 0.74 moles) was slowly added to a reactor containing sulfuric acid (270 g, 99percent, 2.7 moles) at 13 °C, followed by stirring for 0.5 hours and then cooling to 8 °C. To this, oleum (422 g, 31.1percent, 4.61 moles) was added slowly, to obtain a mixture. The mixture comprised resultant sulfuric acid having strength of 104percent. The molar ratio of 3,4-dichloroacetanilide (II) and the resultant sulfuric acid in the mixture was 1: 10. The mixture was further cooled to 3 °C, and nitric acid (51 g, 98percent, 0.79 moles) was slowly added to the mixture over 5 hours. The resultant mixture was further stirred and the progress of the reaction was monitored by thin layer chromatography (TLC). 3,4-Dichloroacetanilide was completely consumed within 1 hour and a product mixture was obtained. The product mixture was carefully poured over 1650 g ice in 200 ml water while maintaining the temperature below 15 °C, followed by stirring for 15 min to obtain a dispersion. The dispersion was filtered to obtain a residue comprising 2-nitro-4,5-dichloroacetanilide (I). The residue was washed with water till it was free of residual acid, and the washed residue was dried to obtain 2-nitro-4,5-dichloroacetanilide (I) (174 g, yield = 95.23percent, HPLC purity = 97.83percent). (0069) HPLC analysis of the product showed the presence of 1.46percent III.
References: [1] Patent: WO2018/91978, 2018, A1, . Location in patent: Page/Page column 7-8; 9.
  • 3
  • [ 95-76-1 ]
  • [ 5462-30-6 ]
References: [1] Journal of Medicinal Chemistry, 1995, vol. 38, # 10, p. 1786 - 1792.
  • 4
  • [ 625-58-1 ]
  • [ 2150-93-8 ]
  • [ 5462-30-6 ]
References: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 31,34, 35.
  • 5
  • [ 108-24-7 ]
  • [ 95-76-1 ]
  • [ 5462-30-6 ]
References: [1] Gazzetta Chimica Italiana, 1977, vol. 107, p. 175 - 180.
 

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