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Chemical Structure| 1953-99-7 Chemical Structure| 1953-99-7

Structure of 1953-99-7

Chemical Structure| 1953-99-7

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Product Details of [ 1953-99-7 ]

CAS No. :1953-99-7
Formula : C8Cl4N2
M.W : 265.91
SMILES Code : C1(=C(C(=C(C(=C1C#N)Cl)Cl)Cl)Cl)C#N
MDL No. :MFCD00019740
InChI Key :OQHXZZGZASQSOB-UHFFFAOYSA-N
Pubchem ID :16057

Safety of [ 1953-99-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H312+H332
Precautionary Statements:P261-P280

Computational Chemistry of [ 1953-99-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 55.91
TPSA ?

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

47.58 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.45
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

3.05
Log Po/w (WLOGP)?

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

4.04
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.

3.03
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

4.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.19

Water Solubility

Log S (ESOL):?

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

-3.73
Solubility 0.0498 mg/ml ; 0.000187 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.

-3.72
Solubility 0.0512 mg/ml ; 0.000193 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

-5.04
Solubility 0.00245 mg/ml ; 0.0000092 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

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.

-5.76 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<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)

1.94

Application In Synthesis of [ 1953-99-7 ]

* 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 [ 1953-99-7 ]

[ 1953-99-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1953-99-7 ]
  • [ 455-32-3 ]
  • [ 1835-65-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; at 270℃; for 16h; A reaction was performed at 270° C. for 16 hours by following the procedure of Example 1 while using 80.0 g (0.301 mol) of 3,4,5,6-tetrachlorophthalonitrile in the place of pentachlorobenzonitrile and 0.1 g of sodium hydroxide in the place of potassium hydroxide. After the reaction was completed, the reaction solution was cooled to room temperature and then filtered to remove the suspended potassium chloride and the unaltered potassium fluoride. When the benzonitrile solution as the mother liquor was analyzed by gas chromatography, it was found to contain 55.4 g of 3,4,5,6-tetrafluorophthalonitrile and 0.018 g of benzoic acid fluoride (325 ppm based on the amount of 3,4,5,6-tetrafluorophthalonitrile). The stainless steel reaction vessel showed no discernible sign of corrosion.
A reaction was performed and the reaction product was treated by following the procedure of Example 1 while omitting the addition of sodium hydroxide. When the benzonitrile solution as the mother liquor was similarly analyzed, it was found to contain 0.200 g of benzoic acid fluoride (3600 ppm based on the amount of 3,4,5,6-tetrafluorophthalonitrile). The stainless steel reaction vessel showed a sign of slight corrosion.
  • 2
  • [ 1953-99-7 ]
  • 3-chloro-4,5,6-trifluoro phthalonitrile [ No CAS ]
  • [ 1835-65-0 ]
  • 3
  • [ 126-33-0 ]
  • [ 1953-99-7 ]
  • [ 1835-65-0 ]
YieldReaction ConditionsOperation in experiment
74% With potassium fluoride; In water; Example A 3,4,5,6-Tetrafluorophthalonitrile Anhydrous potassium fluoride (11.0 kg) is added to a 50 gallon stainless steel reactor. The salt is dried under 28 inches vacuum at 115°-138° C. for 48 hours. The salt is cooled to 100° C. and tetramethylenesulfone (19 liters) added followed by tetrachlorophthalonitrile (4.74 kg). The mixture is heated with stirring to 156° C. over a 30 minute period. Heating with vigorous agitation is continued for another 2.5 hours at 135°-162° C. The mixture was cooled to 31° C. (15 minutes) and ice (69 kg) and demineralized water (119 liters) were added. The resulting mixture was stirred 1.5 hours before centrifuging to collect crude product which was washed with demineralized water (120 liters). The crude product was transferred back into the 50 gallon stainless steel still and demineralized water (100 liters) added. The mixture was steam distilled until 80 liters of distillate were collected. The distillate was cooled to 0°-5° C. and the product collected on a centrifuge. The crystals were washed with demineralized water (2*90 liters) to give 2.82 kg wet product: LOD 6.4percent; calculated yield: 74percent. A small sample was dried under vacuum for two days at room temperature; mp 81°-83° C.
  • 5
  • [ 1953-99-7 ]
  • [ 1835-65-0 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride; In N,N-dimethyl-formamide; at 110℃; for 7h; With molar ratio: tetrachlorophthalonitrile, anhydrous potassium fluoride, N, N-dimethylformamide = 1.0: 4.0: 20.Tetrachlorophthalic phthalonitrile, anhydrous potassium fluoride, N, N-dimethylformamide into chemical reactor, with stirring by increasing the temperature tetrachloro phthalonitrile, anhydrous potassium fluoride was dissolved in N, N-dimethylformamide and the temperature was raised to 110 , maintaining this temperature for 7 hours the stirring was stopped after the reaction, cooling to room temperature, to obtain a liquid mixture; chemical reactor a liquid mixture in a distillation column, the distillate is tetrafluorophthalonitrile, forthwith fed into the dryer, drying at a temperature of 60 for 2.0 hours and then was fed into the drying mill, pulverized into a powder that is finished.
  • 6
  • [ 1953-99-7 ]
  • [ 617-05-0 ]
  • C18H11Cl3N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 12h;Inert atmosphere; Under nitrogen gas, 4,5-dichlorophthalonitrile (5.0 mmol), Ethyl vanillate (7.5 mmol), K2CO3 (50.0 mmol) was dissolved in 30 ml of anhydrous DMF and refluxed at 100 for 12 hours. When the reaction was complete, the reaction solution was slowly dropped on ice-water in a dropwise manner. The precipitate was filtered off under reduced pressure, washed with distilled water, and the dried crude product was purified by column chromatography (eluent: MC: MeOH = 15: 1)
 

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Technical Information

Categories

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