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Structure of 115029-23-7

Chemical Structure| 115029-23-7

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Product Details of [ 115029-23-7 ]

CAS No. :115029-23-7
Formula : C8H4F4O2
M.W : 208.11
SMILES Code : O=C(O)C1=CC(C(F)(F)F)=CC=C1F
MDL No. :MFCD00061292
Boiling Point : No data available
InChI Key :LIFKXWNFWIUMJT-UHFFFAOYSA-N
Pubchem ID :688292

Safety of [ 115029-23-7 ]

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

Computational Chemistry of [ 115029-23-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 38.36
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.28
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

3.2
Log Po/w (WLOGP)?

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

4.12
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.

3.09
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

2.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.87

Water Solubility

Log S (ESOL):?

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

-3.33
Solubility 0.097 mg/ml ; 0.000466 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.

-3.66
Solubility 0.046 mg/ml ; 0.000221 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

-2.94
Solubility 0.237 mg/ml ; 0.00114 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.

-5.3 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.

0.56

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)

1.62

Application In Synthesis of [ 115029-23-7 ]

* 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 [ 115029-23-7 ]

[ 115029-23-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 13220-33-2 ]
  • [ 115029-23-7 ]
  • 2-<(1-methyl-3-pyrrolidinyl)oxy>-5-(trifluoromethyl)benzoic acid sodium salt [ No CAS ]
  • 2
  • [ 115029-23-7 ]
  • [ 207981-46-2 ]
YieldReaction ConditionsOperation in experiment
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h; General procedure: To a suspension of the carboxylic acid (5.00 mmol) in CH2Cl2 (15 mL) was added DMF (2 drops) followed by oxalylchloride (0.530 mL, 6.25 mmol). The reaction mixture was stirred at rt for 4 h, and then evaporated to dryness. Theacid chloride thus prepared was dissolved in CH2Cl2 (15 mL) at 0 C. Triethylamine (2.10 mL, 15.0 mmol) and added,followed by either ethylamine hydrochloride, benzylamine, or 2,4-dimethoxybenzylamine (7.50 mmol). The reactionmixture was allowed to warm to rt and stirred for a further 15 h. Water (50 mL) was added, and the aqueous phaseextracted with CH2Cl2 (3 × 50 mL). The combined organics were washed with saturated Na2CO3 (20 mL), dried overMgSO4, subjected to filtration, and concentrated in vacuo. The crude product was purified by flash chromatographyon silica gel, eluting with EtOAc/hexanes/CH2Cl2, to afford the title compound.
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 3h;Inert atmosphere; To a solution of 2-fluoro-5-trifluoromethylbenzoic acid (500 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was added oxalyl chloride (410 μL, 4.8 mmol) followed by N,N-dimethylformamide (2 drops) and the mixture was stirred at room temperature for 3 hours. The volatiles were removed under a stream of nitrogen and the residue taken up in dichloromethane and added slowly to a solution of 11 (540 mg, 2.4 mmol) and N,N-diisopropylethylamine (1.0 mL, 6.0 mmol) in dichloromethane (10 mL) at 0 C. The mixture was warmed to room temperature and stirred for 4 hours. The mixture was diluted with dichloromethane (30 mL) and washed with saturated aqueous sodium hydrogen carbonate (20 mL) and saturated aqueous ammonium chloride. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by flash column chromatography using ethyl acetate, hexane (0:1 to 3:7) as an eluent to obtain the title compound (660 mg, 67%) as an off-white waxy solid, Rf: 0.45 (2:3 ethyl acetate, hexane); IR (vmax (neat)): 3294, 2962, 1680, 1547, 1326, 1232, 1129, 1092 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.31 (9H, s), 1.62-1.76 (2H, m), 1.80-1.94 (1H, m), 2.00-2.08 (1H, m), 3.68-3.89 (2H, m), 4.11 (1H, dd, J = 15.1, 5.8 Hz), 4.18-4.29 (1H, m), 4.41 (1H, dd, J = 15.4, 1.9 Hz), 6.55 (1H, s), 7.28-7.36 (1H, m), 7.74-7.84 (1H, m), 8.39 (1H, dd, J = 6.9, 2.5 Hz), 10.08 (1H, d, J = 8.1 Hz) ppm; 13C NMR (100 MHz, CDCl3): δ 25.9, 28.1, 30.6, 32.4, 53.0, 68.8, 79.7, 95.6, 117.3 (d, J = 25.3 Hz), 122.4 (d, J = 13.8 Hz), 122.9 (q, J = 272.1 Hz), 128.0 (q, J = 30.3 Hz), 130.1-130.2 (m), 130.7-140.0 (m), 136.4, 159.0 (d, J = 2.8 Hz), 161.0, 161.9 (d, J = 255.2 Hz) ppm; 19F NMR (282 MHz, DMSO-d6): δ -62.3 (CF3), -108.4 (CF) ppm; LRMS (+ESI) m/z: 436.2 ([M+Na]+ 100%), 849.2 ([2M+Na]+ 43%).
With thionyl chloride; at 80℃; for 16h;Inert atmosphere; 2-Fluoro-5-(trifluoromethyl)benzoic acid 7a (382 mg, 1.83 mmol, Shanghai Bide Pharmatech Ltd.) was added to thionyl chloride (5 mL), and the reaction solution was reacted at 80C for 16 hours. The reaction solution was concentrated to obtain the crude title compound 7b (400 mg), which was used directly in the next step without purification.
  • 3
  • [ 146137-78-2 ]
  • [ 115029-23-7 ]
 

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