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Structure of 340825-26-5

Chemical Structure| 340825-26-5

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Product Details of [ 340825-26-5 ]

CAS No. :340825-26-5
Formula : C10H7F3O3
M.W : 232.16
SMILES Code : O=C1CCOC2=C1C=CC(OC(F)(F)F)=C2
MDL No. :MFCD11518472
InChI Key :ROVOVSJXNSHPBD-UHFFFAOYSA-N
Pubchem ID :70922643

Safety of [ 340825-26-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 340825-26-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 47.7
TPSA ?

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

35.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.24
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

2.56
Log Po/w (WLOGP)?

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

3.81
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.

1.17
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

2.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.54

Water Solubility

Log S (ESOL):?

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

-3.04
Solubility 0.213 mg/ml ; 0.000917 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.

-2.95
Solubility 0.258 mg/ml ; 0.00111 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

-3.49
Solubility 0.075 mg/ml ; 0.000323 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.

-5.9 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

0.0 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)

2.16

Application In Synthesis of [ 340825-26-5 ]

* 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 [ 340825-26-5 ]

[ 340825-26-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 827-99-6 ]
  • [ 625-36-5 ]
  • [ 340825-26-5 ]
YieldReaction ConditionsOperation in experiment
39% A solution of <strong>[827-99-6]3-(trifluoromethoxy)phenol</strong> (7.13 mL, 55.0 mmol) and 3-chloropropanoyl chloride (5.5 mL, 57.6 mmol) in trifluoroacetic acid (25 mL) was stirred 15 minutes at ambient temperature, and then heated at 50° C. for 90 minutes. After stirring at ambient temperature overnight, the solution was added over 5 minutes to preheated triflic acid (20 mL) at 50° C. After 20 minutes, the mixture was removed from the oil bath, then cooled in an ice water bath. Crushed ice was added, slowly at first, keeping the temperature of the orange solution below 25° C. Eventually a solid precipitate formed, and the suspension was diluted with MTBE (200 mL). The mixture was cooled in an ice water bath. It was washed with brine and then four times with water, partially dried (Na2SO4), filtered, and concentrated. After standing overnight, the yellow mixture was dissolved in ethanol (180 mL) and added slowly over 22 minutes to 1.5 M aqueous Na2CO3 (180 mL) cooled with a water ice bath (internal temp did not exceed 15° C.). The suspension was permitted to come to ambient temperature overnight, and was then diluted with 2:1 EtOAc/hexanes (300 mL) and filtered. The solids were rinsed with more 2:1 solution (105 mL), and the aqueous phase of the filtrate was separated and extracted with 1:1 EtOAc/hexanes (3*100 mL). The combined organic phases were washed once with water (200 mL), and the aqueous phase was back-extracted once with 1:1 solution (40 mL). The organic phases were combined and washed with brine (30 mL), dried (Na2SO4), filtered, and concentrated, chromatographed on silica (gradient elution, 5-20percent Et2O/hexanes) to give the title compound (4.95 g, 21.3 mmol, 39percent yield). 1H NMR (300 MHz, DMSO-d6) delta 7.90-7.85 (m, 1H), 7.08-7.01 (m, 2H), 4.61 (dd, 2H), 2.83 (dd, 2H).
 

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