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Chemical Structure| 320-47-8 Chemical Structure| 320-47-8

Structure of 320-47-8

Chemical Structure| 320-47-8

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Product Details of [ 320-47-8 ]

CAS No. :320-47-8
Formula : C8H3F3N2O2
M.W : 216.12
SMILES Code : [O-][N+](=O)C1=CC(=C(C=C1)C#N)C(F)(F)F
MDL No. :MFCD01075729
InChI Key :AGKQJEFSEQHGTA-UHFFFAOYSA-N
Pubchem ID :2775783

Safety of [ 320-47-8 ]

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

Computational Chemistry of [ 320-47-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 44.98
TPSA ?

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

69.61 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.13
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

2.35
Log Po/w (WLOGP)?

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

3.64
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.

2.14
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

0.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.0

Water Solubility

Log S (ESOL):?

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

-2.82
Solubility 0.324 mg/ml ; 0.0015 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.

-3.45
Solubility 0.0764 mg/ml ; 0.000354 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

-2.76
Solubility 0.377 mg/ml ; 0.00175 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.

-5.95 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)

2.11

Application In Synthesis of [ 320-47-8 ]

* 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 [ 320-47-8 ]

[ 320-47-8 ] Synthesis Path-Downstream   1~22

  • 1
  • [ 320-47-8 ]
  • [ 320-37-6 ]
YieldReaction ConditionsOperation in experiment
With water; sodium hydroxide; In ethanol; at 80℃; First, NaOH (5.88 g, 0.147 mol) was dissolved in ethanol/DI water (1:1) 400 ml in a 3-neck reaction flask, and then the <strong>[320-47-8]2-cyano-5-nitrobenzotrifluoride</strong> (9.34 g, 0.0368 mol) synthesized above was added thereto. The resulting solution was refluxed at 80 C. overnight to synthesize 4-nitro-2-(trifluoromethyl)benzoic acid (B). After the reaction, the solution was cooled again to room temperature and then ethanol was evaporated followed by neutralizing thereof with 1N aqueous HCl solution. Then, the precipitated solid was filtered through a filter paper. The solid was washed with a small amount of DI water to obtain 4-nitro-2-(trifluoromethyl)benzoic acid.
  • 3
  • diazotized 4-nitro-2-trifluoromethyl-aniline [ No CAS ]
  • [ 320-47-8 ]
  • 5
  • [ 367-67-9 ]
  • [ 544-92-3 ]
  • [ 320-47-8 ]
  • 6
  • [ 320-47-8 ]
  • 4-dodecyloxy-2-trifluoromethylbenzamide [ No CAS ]
  • 8
  • potassium tetracyanonickelate (K2 NiCN4) [ No CAS ]
  • [ 121-01-7 ]
  • [ 320-47-8 ]
YieldReaction ConditionsOperation in experiment
6.8 g (65%) With hydrogenchloride; sodium nitrite; In water; sodium hydrogencarbonate; acetic acid; a. 2-Cyano-5-nitrobenzotrifluoride A solution of 10.0 g (48.5 mmol) 2-amino-5-nitrobenzotrifluoride in 60 ml glacial acetic acid was added 200 ml 2N hydrochloric acid, and then at 0 C. diazotized with a solution of 3.36 g (48.6 mmol) sodium nitrite in 100 ml water. Stirring was continued at 0 C. for 1 h, and then at 25 C. a solution of 18 g (75 mmol) potassium tetracyanonickelate (K2 NiCN4) in 500 ml saturated sodium hydrogencarbonate was added dropwise. Extraction with ethyl acetate followed by distillation (95-100 C./0.5 mmHg) of the crude oil gave 6.8 g (65%) of 2-cyano-5-nitrobenzotrifluoride.
  • 9
  • [ 55895-85-7 ]
  • [ 320-47-8 ]
  • [ 22227-54-9 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In acetic acid; The diethyl glutamate used as starting material was obtained as follows:- A mixture of <strong>[320-47-8]4-nitro-2-trifluoromethylbenzonitrile</strong> (J.Amer.Chem.Soc. 1954, 76 , 1051; 5.6 g), glacial acetic acid (20 ml) and sulphuric acid (concentrated, 30 ml) was stirred and heated to 130C for 45 minutes. The mixture was cooled, poured onto ice (100 ml) and extracted with ethyl acetate (3 x 150 ml). The combined extracts were washed with aqueous 0.05N-hydrochloric acid solution, dried over sodium sulphate, filtered and evaporated. The residue was purified by chromatography on a silica gel column using ethyl acetate as eluent. There was thus obtained 4-nitro-2-trifluoromethylbenzamide (5.16 g), m.p. 192C.
  • 10
  • [ 121-01-7 ]
  • [ 151-50-8 ]
  • [ 320-47-8 ]
  • 11
  • [ 111-87-5 ]
  • [ 320-47-8 ]
  • [ 1094279-18-1 ]
  • 12
  • [ 112-30-1 ]
  • [ 320-47-8 ]
  • [ 1132110-15-6 ]
  • 13
  • [ 112-72-1 ]
  • [ 320-47-8 ]
  • [ 1132110-16-7 ]
  • 14
  • [ 36653-82-4 ]
  • [ 320-47-8 ]
  • [ 1132110-17-8 ]
  • 15
  • [ 320-47-8 ]
  • 4-nitro-2-(trifluoromethyl)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
4-Nitro-2-(trifluoromethyl) benzaldehyde (D30) To <strong>[320-47-8]4-nitro-2-(trifluoromethyl)benzonitrile</strong> (100 mg, 0.463 mmol) in toluene (3 ml.) at 0 0C under argon was added DIBAL-H (0.51 ml_, 1 M in toluene, 0.51 mmol) and the reaction stirred for 3.75 h. MeOH and sulphuric acid were added and the reaction mixture was warmed to room temperature and stirred for 1 h. The mixture was concentrated and the residue was portioned between EtOAc (10 ml.) and water (10 ml_). The organic phase was dried and concentrated to give the crude product which was purified by column chromatography eluting with 0-15% EtOAc/petroleum ether to give the title compound as a yellow oil (91 mg), deltaH (CDCI3, 400MHz) 10.47 (1 H, s), 8.66 (1 H, d), 8.56 (1 H, dd), 8.33 (1 H, d).
  • 16
  • [ 320-47-8 ]
  • [ 29654-55-5 ]
  • [ 1056028-31-9 ]
  • 17
  • [ 320-47-8 ]
  • [ 13036-02-7 ]
  • [ 1222257-58-0 ]
  • 18
  • [ 320-47-8 ]
  • [ 100-52-7 ]
  • C15H9F3N2O [ No CAS ]
  • 19
  • [ 320-47-8 ]
  • 1-(4-cyano-3-trifluoromethylphenyl)-4-phenyl-2-azetidinone [ No CAS ]
  • 20
  • [ 320-47-8 ]
  • C15H7F6N3O5 [ No CAS ]
  • 21
  • [ 320-47-8 ]
  • C15H11F6N3O [ No CAS ]
  • 22
  • [ 367-67-9 ]
  • copper(l) cyanide [ No CAS ]
  • [ 320-47-8 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 160℃; for 18h;Inert atmosphere; 2-Bromo-5-nitrobenzo trifluoride (20 g, 0.111 mol) and CuCN (12 g, 0.134 mol) were dissolved in a 250 ml 3-neck reaction flask containing DMF (90 ml), respectively. Then, the solution was refluxed at 160 C. for 18 hours at nitrogen atmosphere to synthesize 2-cyano-5-nitrobenzotrifluoride (A). Then, the reactant was cooled to room temperature and homogeneously mixed with a pre-made workup solution (FeCl3 50 g, conc. HCl 30 ml, DI water 500 ml). The mixture was extracted with ethyl acetate and subjected to fractional washing with 10% (v/v) aqueous HCl solution followed by evaporating the ethyl acetated by using a rotary evaporator. Finally, dark brown liquid was obtained, and the solvent remained in the brown liquid was evaporated and removed in a 80 C. vacuum oven to obtain 2-cyano-5-nitrobenzotrifluoride.
 

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