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Chemical Structure| 657-02-3 Chemical Structure| 657-02-3

Structure of 657-02-3

Chemical Structure| 657-02-3

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Product Details of [ 657-02-3 ]

CAS No. :657-02-3
Formula : C7H2Cl2F3NO2
M.W : 260.00
SMILES Code : [O-][N+](=O)C1=CC(=CC(Cl)=C1Cl)C(F)(F)F
MDL No. :MFCD01862035
InChI Key :FZHCKUHPOZBPHB-UHFFFAOYSA-N
Pubchem ID :2774030

Safety of [ 657-02-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P264-P270-P301+P312-P330

Computational Chemistry of [ 657-02-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 50.29
TPSA ?

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

45.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.51
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

3.3
Log Po/w (WLOGP)?

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

5.07
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.

3.91
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

2.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.17

Water Solubility

Log S (ESOL):?

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

-3.69
Solubility 0.0525 mg/ml ; 0.000202 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.

-3.94
Solubility 0.03 mg/ml ; 0.000115 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

-3.9
Solubility 0.0327 mg/ml ; 0.000126 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.

-5.54 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)

2.01

Application In Synthesis of [ 657-02-3 ]

* 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 [ 657-02-3 ]

[ 657-02-3 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 328-84-7 ]
  • [ 657-02-3 ]
YieldReaction ConditionsOperation in experiment
18% With sulfuric acid; nitric acid; (a) 3,4-Dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene 3,4-Dichloro-alpha,alpha,alpha-trifluorotoluene (862 g. 4.0 mols) is added to a stirred mixture of concentrated sulfuric acid (4400 g.) and nitric acid (3400 g.) at 35 C. The mixture is stirred 70 minutes at 95 C. and allowed to separate. The oil layer is washed once with water and twice with 5% sodium carbonate solution, dried, and fractionally distilled to give 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 18%) b.p. 115-118 C./15 mm, 88% pure.
18% With sulfuric acid; nitric acid; a. 3.4-Dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene 3,4-Dichloro-alpha,alpha,alpha-trifluorotoluene (862 g. 4.0 mols) is added to a stirred mixture of concentrated sulfuric acid (4400 g.) and nitric acid (3400 g.) at 35 C. The mixture is stirred 70 minutes at 95 C. and allowed to separate. The oil layer is washed once with water and twice with 5% sodium carbonate solution, dried, and fractionally distilled to give 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 18%) b.p. 115-118 C./15 mm, 88% pure.
18% With sulfuric acid; nitric acid; a. 3,4-Dichloro-5-nitro-alpha,alpha,alpha -trifluorotoluene 3,4-Dichloro-alpha,alpha,alpha-trifluorotoluene (862 g. 4.0 mols) is added to a stirred mixture of concentrated sulfuric acid (4400 g.) and nitric acid (3400 g.) at 35 C. The mixture is stirred 70 minutes at 95 C, and allowed to separate. The oil layer is washed once with water and twice with 5% sodium carbonate solution, dried, and fractionally distilled to give 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 18%) b.p. 115-118 C./15 mm, 88% pure.
18% With sulfuric acid; nitric acid; a. 3,4-Dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene 3,4-Dichloro-alpha,alpha,alpha-trifluorotoluene (862 g. 4.0 mols) is added to a stirred mixture of concentrated sulfuric acid (4400 g.) and nitric acid (3400 g.) at 35 C. The mixture is stirred 70 minutes at 95 C. and allowed to separate. The oil layer is washed once with water and twice with 5% sodium carbonate solution, dried, and fractionally distilled to give 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 18%) b.p. 115-118 C./15 mm, 88% pure.
18% With sulfuric acid; nitric acid; a. 3,4-Dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene 3,4-Dichloro-alpha,alpha,alpha-trifluorotoluene (862 g. 4.0 mols) is added to a stirred mixture of concentrated sulfuric acid (4400 g.) and nitric acid (3400 g.) at 35 C. The mixture is stirred 70 minutes at 95 C. and allowed to separate. The oil layer is washed once with water and twice with 5% sodium carbonate solution, dried, and fractionally distilled to give 3,4dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 18%) b.p. 115-118 C./15 mm, 88% pure.

  • 3
  • [ 657-02-3 ]
  • [ 50594-81-5 ]
YieldReaction ConditionsOperation in experiment
78% (b) 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene 500 ml. of an ethanolic solution containing 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 0.72 mol), and platinum oxide (Adam's catalyst) (0.2 g.) is reduced at room temperature in a low pressure hydrogenation apparatus to give 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (129.9 g. 78%) b.p. 65-70 C./1-2 mm.
78% (b) 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene 600 ml. of an ethanolic solution containing 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 0.72 mol), and platinum oxide (Adam's catalyst) (0.2 g.) is reduced at room temperature in a low pressure hydrogenation apparatus to give 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (129.9 g. 78%) b.p. 65-70 C./1-2 mm.
78% (b) 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene 500 ml. of an ethanolic solution containing 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 0.72 mol), and platinum oxide (Adam's catalyst) (0.2 g.) is reduced at room temperature in a low pressure hydrogenation apparatus to give 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (129.9 g. 78% b.p. 65-70 C./1-2 mm.
78% b. 5-Amino-3,4-dichloro-alpha,alpha,alpha -trifluorotoluene 500 ml. of an ethanolic solution containing 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 0.72 mol), and platinum oxide (Adam's catalyst) (0.2 g.) is reduced at room temperature in a low pressure hydrogenation apparatus to give 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (129.9 g. 78%) b.p. 65-70 C./1-2 mm.
78% b. 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene 500 ml. of an ethanolic solution containing 3,4-dichloro-5-nitro-alpha,alpha,alpha-trifluorotoluene (188 g. 0.72 mol), and platinum oxide (Adam's catalyst) (0.2 g.) is reduced at room temperature in a low pressure hydrogenation apparatus to give 5-Amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (129.9 g. 78%) b.p. 65-70 C./1-2 mm.

  • 4
  • [ 657-02-3 ]
  • [ 108-95-2 ]
  • [ 50594-32-6 ]
  • 5
  • [ 328-84-7 ]
  • [ 657-02-3 ]
  • 3,4-dichloro-6-nitro-benzotrifluoride [ No CAS ]
  • 9
  • [ 657-02-3 ]
  • [ 42874-36-2 ]
  • 10
  • [ 657-02-3 ]
  • [ 50594-34-8 ]
  • 11
  • [ 657-02-3 ]
  • [ 50594-33-7 ]
  • 12
  • [ 657-02-3 ]
  • [ 101646-02-0 ]
YieldReaction ConditionsOperation in experiment
67% With potassium fluoride; tetramethlyammonium chloride; (B) The 3-chloro-4-fluoro-5-nitrobenzotrifluoride starting reactant employed in the above example was prepared in the follow manner. A mixture of 52 parts of <strong>[657-02-3]3,4-dichloro-5-nitrobenzotrifluoride</strong>, 16.2 parts of anhydrous potassium fluoride and 2.5 parts of tetramethylammonium chloride was heated and maintained at about 120 to 140 C. for about 7 hours. The mixture was then cooled to room temperature, diluted with methylene chloride, and filtered. The filtrate was distilled to yield 35.2 parts (67% yield) of 3-chloro-4-fluoro-5-nitrobenzotrifluoride. The structure of the product was confirmed by gas chromatography-mass spectrum analysis.
  • 13
  • [ 657-02-3 ]
  • [ 108-95-2 ]
  • 2-chloro-α,α,α-trifluoro-6-nitro-p-tolylphenyl ether [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In sulfolane; water; b. 2-Chloro-alpha,alpha,alpha-trifluoro-6-nitro-p-tolylphenyl ether A solution of potassium hydroxide (43.2 g. of 86% pure, 0.665 moles) in water (20 ml.) was added slowly to a mixture of phenol (62.5 g., 0.665 mole) and the product from (a) above 450 g. total, equivalent to 0.665 mole of 3,4-dichloro-alpha,alpha,alpha-trifluoro-5-nitro toluene) in sulfolane (300 ml.) at 30-68 C. with stirring. After stirring at 42-68 C for a total of one hour the mixture was diluted with hexane (400 ml.) and water (600 ml.). The resulting layers were separated and the aqueous phase extracted once with hexane. The combined organic phases were washed with water and dilute caustic soda solution, dried and the solvent removed. The residue (471.3 g.) was distilled through a vacuum jacketed Vigreux column. No. 1 (272.2 g.) bp < 100 C/0.2 mm. consisted essentially of unreacted 3,4-dichloro-alpha,alpha,alpha-trifluoro-6-nitrotoluene. No. 2 (196.2 g.) b.p. 109-119 C/0.2 mm. was essentially pure desired diphenylether. A small residue (3.5 g.) was discarded. No. 2 crystallized and was recrystallized from 2-propanol (600 ml.) at 0 C. to give 2-chloro-alpha,alpha,alpha-trifluoro-6-nitro-p-tolylphenyl ether (144 g. 68%) m.p. 57-61 C.
With potassium hydroxide; In sulfolane; water; b. 2-Chloro-alpha,alpha,alpha-trifluoro-6-nitro-p-tolylphenyl ether A solution of potassium hydroxide (43.2 g. of 86% pure, 0.665 moles) in water (20 ml.) was added slowly to a mixture of phenol (62.5 g., 0.665 mole) and the product from (a) above 450 g. total, equivalent to 0.665 mole of 3,4-dichloro-alpha,alpha,alpha-trifluoro-5-nitro toluene) in sulfolane (300 ml.) at 30-68 C. with stirring. After stirring at 42-68 C. for a total of one hour the mixture was diluted with hexane (400 ml.) and water (600 ml.). The resulting layers were separated and the aqueous phase extracted once with hexane. The combined organic phases were washed with water and dilute caustic soda solution, dried and the solvent removed. The residue (471.3 g.) was distilled through a vacuum jacketed Vigreux column. No. 1 (272.2 g.) bp<100 C./0.2 mm. consisted essentially of unreacted 3,4-dichloro-alpha,alpha,alpha-trifluoro-6-nitrotoluene. No. 2 (196.2 g.) b.p. 109-119 C./0.2 mm. was essentially pure desired diphenylether. A small residue (3.5 g.) was discarded. No. 2 crystallized and was recrystallized from 2-propanol (600 ml.) at 0 C. to give 2-chloro-alpha,alpha,alpha-trifluoro-6-nitro-p-tolylphenyl ether (144 g. 68%) m.p. 57-61 C.
  • 14
  • [ 657-02-3 ]
  • [ 5197-95-5 ]
  • [ 69741-64-6 ]
YieldReaction ConditionsOperation in experiment
77% With sodium hydroxide; In methanol; water; EXAMPLE 3 50 g of 3,4-dichloro-5-nitro-benzotrifluoride and 5 g of benzyltriethylammonium bromide are initially introduced into 150 ml of methanol, and 100 g of 50% strength sodium hydroxide solution are added dropwise at 25 to 30 C. The mixture is then stirred at 65 C. for a further 4 hours and cooled, 100 ml of water are added and the mixture is rendered acid with sulphuric acid. The crude product is extracted with methylene chloride, the solution is dried and the methylene chloride is distilled off. The residue is subjected to fractional distillation and 35 g of 2-chloro-4-trifluoromethyl-6-nitrophenol with a boiling point of 74 to 76 C. under 0.25 mm are obtained. Melting point: 33-34 C. from hexane. Yield: 77% of theory.
  • 15
  • [ 657-02-3 ]
  • [ 57729-79-0 ]
YieldReaction ConditionsOperation in experiment
98.1% With ammonia; at 200.0℃;Large scale; To the reactor was added <strong>[657-02-3]3,4-dichloro-5-nitrobenzotrifluoride</strong> 600Kg, airtight reactor, nitrogen substitution, open stirring, gradually warmed to 200 C, gradually through the ammonia gas,To pass into the amount of 125Kg, the sampling tube sampling and detection of <strong>[657-02-3]3,4-dichloro-5-nitrobenzotrifluoride</strong> 0.3%, cooled to below 80 C, venting ammonia gas to the tail gas recovery unit, the kettle 200Kg * 2 washing,The organic layer was washed with saturated brine and dehydrated under reduced pressure to obtain 544 kg of the obtained product (yield: 99.1%, water: 0.5%, yield: 98.1%).
 

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