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Chemical Structure| 168966-54-9

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Product Details of [ 168966-54-9 ]

CAS No. :168966-54-9
Formula : C6H5F3N2
M.W : 162.11
SMILES Code : NC1=CC(F)=C(F)C(F)=C1N
MDL No. :MFCD01569524
InChI Key :WWDBSPRMQHYOOQ-UHFFFAOYSA-N
Pubchem ID :2773958

Safety of [ 168966-54-9 ]

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

Computational Chemistry of [ 168966-54-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 35.12
TPSA ?

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

52.04 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.11
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

0.86
Log Po/w (WLOGP)?

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

2.54
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.

2.12
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

1.7
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-1.79
Solubility 2.63 mg/ml ; 0.0162 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.54
Solubility 4.71 mg/ml ; 0.0291 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

-2.51
Solubility 0.504 mg/ml ; 0.00311 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

No
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.

-6.68 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

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)

1.31

Application In Synthesis of [ 168966-54-9 ]

* 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 [ 168966-54-9 ]

[ 168966-54-9 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 144-62-7 ]
  • [ 168966-54-9 ]
  • [ 170098-76-7 ]
  • 2
  • [ 148416-38-0 ]
  • [ 168966-54-9 ]
YieldReaction ConditionsOperation in experiment
70% With hydrogenchloride; tin; for 1.5h;Reflux; Concentrated HCl (15 mL) was slowly added dropwise to a mixture of nitroaniline 8, 13c-d (12 mmol), and tin (30 mmol). The reactionmixture was heated at reflux for 1.5 h, cooled to r.t., and neutralizedwith 50% NaOH solution to pH 9-10. The precipitate was filtered off,dried, and extracted with hot EtOAc (80 mL). Diamines 10 and 14c-dwere obtained after evaporation of filtrates.3,4,5-Trifluoro-1,2-phenylenediamine (10)Yield: 1.40 g (70%); brown crystals; mp 85-87 C; Rf 0.72
  • 3
  • [ 168966-54-9 ]
  • [ 76-05-1 ]
  • 4,5,6-trifluoro-2-trifluoromethyl-1<i>H</i>-benzoimidazole [ No CAS ]
  • 4
  • [ 3862-73-5 ]
  • [ 168966-54-9 ]
  • 5
  • [ 365-29-7 ]
  • [ 168966-54-9 ]
  • 6
  • 1,2,3-Trifluoro-6-nitroaniline [ No CAS ]
  • [ 168966-54-9 ]
YieldReaction ConditionsOperation in experiment
76% aluminum nickel; In ethanol; water; hydrogen; A. 3,4,5-Trifluoro-1,2-phenylenediamine 1,2,3-Trifluoro-6-nitroaniline (15.0 g, 78.1 mmol, Aldrich, Milwaukee), Raney nickel (Aldrich, Milwaukee, slurry in water, 1.0 g wet) and ethanol (100 mL) were placed in a Parr reactor which was pressurized with hydrogen (175 psig) and stirred. The resulting mixture was allowed to stir overnight at rt, after which time it was filtered through Celite and the solvents were removed in vacuo to provide a dark oil. The title compound was purified by silica gel chromatography using 3:2 hexane-ethyl acetate as eluent to provide a brown solid (9.6 g, 76%); 1H NMR (DMSO-d6) delta: 6.30 (m, 1 H, Ar-H), 4,91 (br s, 2H, NH2), 4.52 (br s, 2H, NH2).
  • 7
  • tin(II)chloride dihydrate [ No CAS ]
  • [ 64-17-5 ]
  • [ 365-29-7 ]
  • [ 148416-38-0 ]
  • [ 168966-54-9 ]
YieldReaction ConditionsOperation in experiment
285 mg (25%) With KNO3; sulfuric acid; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethyl acetate; 3,4,5-Trifluoro-1,2-phenylenediamine. To 2,3,4-trifluoroacetanilide (1.35 g, 7.09 mmol) is added concentrated sulfuric acid (8 mL). While the flask is in an ice bath, KNO3 is slowly added, giving a tan mixture, that is stirred overnight. The reaction mixture, now dark red, is then added to ice water (45 mL), instantly giving an orange precipitate. The volatile compound, presumably 2,3,4-trifluoro-6-nitroaniline, is dissolved in ethyl acetate (18 mL) and ethyl alcohol (12 mL). To the orange solution is added stannous chloride dihydrate (7.6 g, 34 mmol). The resulting mixture is stirred and brought to reflux under N2 for 4 h. The mixture is added to ice water (40 mL) and basified with 2N NaOH (40 mL). It is extracted with ethyl acetate (3*20 mL) and the combined extracts are washed with water (20 mL) and brine (20 mL). This dark red solution is dried (MgSO4) and evaporated to give 285 mg (25%) of the diamine as a dark red solid. 1 H NMR (CDCl3), 3.22 (br s, 2H), 3.46 (br s, 2H), 6.32 (m, 1H).
285 mg (25%) With KNO3; sulfuric acid; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethyl acetate; 3,4,5-Trifluoro-1,2-phenylenediamine To 2,3,4-trifluoroacetanilide (1.35 g, 7.09 mmol) is added concentrated sulfuric acid (8 mL). While the flask is in an ice bath, KNO3 was slowly added, giving a tan mixture, which was stirred overnight. The reaction mixture, now dark red, was then added into ice water (45 mL), instantly giving an orange precipitate. The volatile compound, presumably 2,3,4-trifluoro-6-nitroaniline, is dissolved in ethyl acetate (18 mL) and ethyl alcohol (12 mL). To the orange solution is added stannous chloride dihydrate (7.6 g, 34 mmol). The resulting mixture is stirred and brought to reflux under N2 for 4 h. The mixture is added into ice water (40 mL) and basified with 2N NaOH (40 mL). It was extracted with ethyl acetate (3*20 mL) and the combined extracts were washed with water (20 mL) and brine (20 mL). This dark red solution is dried (MgSO4) and evaporated to give 285 mg (25%) of the diamine as a dark red solid. 1 H NMR (CDCl3), 3.22 (br s, 2H), 3.46 (br s, 2H), 6.32 (m, 1H).
  • 8
  • [ 168966-54-9 ]
  • [ 170098-76-7 ]
YieldReaction ConditionsOperation in experiment
15 mg (36%) With oxalic acid; In hydrogenchloride; ethanol; 5,6,7-Trifluoro-1,4-dihydro-2,3-quinoxalinedione. To a brown solution of <strong>[168966-54-9]3,4,5-trifluoro-1,2-phenylenediamine</strong> (285 mg, 1.75 mmol) in aqueous 2N HCl (10 mL) is added oxalic acid (221 mg, 1.75 mmol). The brown mixture is brought to reflux and stirred under N2 overnight. The mixture is filtered to yield 139 mg (37%) of crude title compound. An analytical sample is prepared by dissolving 42 mg of this brown powder in 2.5 mL boiling ethanol. Upon cooling, brown, rod-like, crystals are formed, which are filtered and dried in vacuo to yield 15 mg (36%) of pure title compound: 1 H NMR (DMSO-d6), 6.91 (m, 1H), 12.02 (s, 1H), 12.19 (s, 1H); analysis calculated for C8 H3 F3 N2 O2: C, 44.46; H, 1.40; N, 12.96. Found: C, 44.42; H, 1.16; N, 12.76.
15 mg (36%) With oxalic acid; In hydrogenchloride; ethanol; 5,6,7-Trifluoro-1,4-dihydro-2,3-quinoxalinedione To a brown solution of <strong>[168966-54-9]3,4,5-trifluoro-1,2-phenylenediamine</strong> (285 mg, 1.75 mmol) in aqueous 2N HCl (10 mL) is added oxalic acid (221 mg, 1.75 mmol). The brown mixture is brought to reflux and stirred under N2 overnight. The mixture is filtered to yield 139 mg (37%) of crude title compound. An analytical sample is prepared by dissolving 42 mg of this brown powder in 2.5 mL boiling ethanol. Upon cooling, brown rod-like crystals were formed which are filtered and dried in vacuo to yield 15 mg (36%) of pure title compound: 1 H NMR (DMSO-d6), 6.91 (m, 1H), 12.02 (s, 1H), 12.19 (s, 1H); analysis calculated for C8 H3 F3 N2 O2: C, 44.46; H, 1.40; N, 12.96. Found: C, 44.42; H, 1.16; N, 12.76.
  • 9
  • C17H24ClF3O2Si [ No CAS ]
  • [ 168966-54-9 ]
  • C23H26F6N2OSi [ No CAS ]
  • 10
  • [ 882068-89-5 ]
  • [ 168966-54-9 ]
  • 11
  • [ 100-52-7 ]
  • [ 168966-54-9 ]
  • [ 1196131-58-4 ]
  • 12
  • [ 64-18-6 ]
  • [ 168966-54-9 ]
  • C8H6F2N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% for 4.0h;Reflux; General procedure: Compounds 10 and 14a-d (6 mmol) were heated at reflux in formicacid (30 mL) for 4 h. The reaction mixture was then evaporated undervacuum, poured into H2O (50 mL) and neutralized with a 10% solutionof NaOH (20 mL) to pH 7. The precipitate was filtered off, dried, andrecrystallized from a mixture H2O-MeCN (1:1).
  • 13
  • [ 168966-54-9 ]
  • 6,7,8-trifluoro-5-nitro-1,4-dihydroquinoxaline-2,3-dione [ No CAS ]
 

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