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Chemical Structure| 81565-19-7 Chemical Structure| 81565-19-7

Structure of 81565-19-7

Chemical Structure| 81565-19-7

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Product Details of [ 81565-19-7 ]

CAS No. :81565-19-7
Formula : C6H3ClF3N
M.W : 181.54
SMILES Code : FC(F)(F)C1=C(Cl)C=NC=C1
MDL No. :MFCD07368053
InChI Key :YNYROPYZSZBORI-UHFFFAOYSA-N
Pubchem ID :12140226

Safety of [ 81565-19-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 81565-19-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 34.25
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.68
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

2.36
Log Po/w (WLOGP)?

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

3.91
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.

2.18
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

3.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.63

Water Solubility

Log S (ESOL):?

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

-2.79
Solubility 0.294 mg/ml ; 0.00162 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.

-2.27
Solubility 0.973 mg/ml ; 0.00536 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

-3.53
Solubility 0.0541 mg/ml ; 0.000298 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.

-5.73 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

2.0
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)

1.38

Application In Synthesis of [ 81565-19-7 ]

* 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 [ 81565-19-7 ]

[ 81565-19-7 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 75-77-4 ]
  • [ 81565-19-7 ]
  • [ 796090-26-1 ]
  • 2
  • [ 77332-79-7 ]
  • [ 81290-20-2 ]
  • [ 81565-19-7 ]
  • 3
  • [ 124-38-9 ]
  • [ 81565-19-7 ]
  • 3-chloro-4-(trifluoromethyl)pyridine-2-carboxylic acid [ No CAS ]
  • 4
  • [ 77332-79-7 ]
  • [ 81565-19-7 ]
YieldReaction ConditionsOperation in experiment
(2) 3-Chloro-4-trifluoromethylpyridine was obtained from 3- chloro-4-iodopgammaridine by the method described in Eur. J. Org. Chem., (2004), 3793.
  • 5
  • [ 81565-19-7 ]
  • 3-chloro-4-(trifluoromethyl)pyridine-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
(3) The title compound was obtained from 3-chloro-4- trifluoromethylpyridine by the method described in Eur . J . Org . Chem., (2004), 3793.
  • 6
  • [ 81565-19-7 ]
  • 5-chloro-4-(trifluoromethyl)pyridine-2-carboxylic acid [ No CAS ]
  • 7
  • [ 81565-19-7 ]
  • 5-chloro-4-(trifluoromethyl)pyridine-3-carboxylic acid [ No CAS ]
  • 8
  • [ 81565-19-7 ]
  • [ 796090-30-7 ]
  • 9
  • [ 81565-19-7 ]
  • [ 796090-29-4 ]
  • 10
  • [ 81565-19-7 ]
  • [ 1026008-61-6 ]
  • 11
  • [ 81565-19-7 ]
  • [ 1026187-48-3 ]
  • 12
  • [ 1276039-75-8 ]
  • [ 81565-19-7 ]
  • [ 1276034-56-0 ]
  • 13
  • [ 81565-19-7 ]
  • 3-chloro-4-(trifluoromethyl)pyridine 1-oxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With dihydrogen peroxide; acetic acid; at 80℃; Step A. 3-Chloro-4-(trifluoromethyl)pyridine 1-oxide A mixture of <strong>[81565-19-7]3-chloro-4-(trifluoromethyl)pyridine</strong> (2.00 g, 11.0 mmol) and H2O2 (3.2 mL, 31 mmol) in AcOH (6 mL) was stirred at 80 C. overnight. The reaction mixture was allowed to cool to ambient temperature and quenched with NaHSO3 solution. The mixture was concentrated under reduced pressure and the residue was added saturated NaHCO3 solution (30 mL). The resulting mixture was extracted with DCM (3 times). The combined organic phases were washed with aq. NaHCO3, water and brine, dried over Na2SO4 and concentrated under reduced pressure to give 2.11 g (97% yield) of the sub-title compound as a pink solid. LCMS calc. for C6H4ClF3NO (M+H)+: m/z=198.0. found: 198.0.
  • 14
  • [ 81565-19-7 ]
  • 3-chloro-4-(trifluoromethyl)pyridine-2-carbonitrile [ No CAS ]
  • 15
  • [ 81565-19-7 ]
  • methyl 3-amino-7-(trifluoromethyl)thieno[3,2-b]pyridine-2-carboxylate [ No CAS ]
  • 16
  • [ 81565-19-7 ]
  • ethyl 3-(5-butoxy-4-(trifluoromethyl)pyridin-2-yl)propanoate [ No CAS ]
  • 17
  • [ 81565-19-7 ]
  • ethyl 3-(5-morpholino-4-(trifluoromethyl)pyridin-2-yl)propanoate [ No CAS ]
  • 18
  • [ 140-88-5 ]
  • [ 81565-19-7 ]
  • ethyl 3-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)propanoate [ No CAS ]
  • diethyl 3,3'-(3-chloro-4-(trifluoromethyl)pyridine-2,6-diyl)dipropanoate [ No CAS ]
  • 19
  • [ 2680-03-7 ]
  • [ 81565-19-7 ]
  • 2-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)-N,N-dimethylpropanamide [ No CAS ]
  • 20
  • [ 110-91-8 ]
  • [ 81565-19-7 ]
  • 4-(4-(trifluoromethyl)pyridin-3-yl)morpholine [ No CAS ]
  • 21
  • [ 71-36-3 ]
  • [ 81565-19-7 ]
  • 3-butoxy-4-(trifluoromethyl)pyridine [ No CAS ]
  • 22
  • [ 158063-66-2 ]
  • [ 81565-19-7 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; In toluene; at 50 - 80℃; for 3h; In a 250 ml four-necked flask equipped with a reflux condenser, a thermometer and a dropping funnel, 30.0 g (0.157 mol) of 4-(trifluoromethyl)nicotinic acid, 100 ml of toluene, heated to 50-60 C, and dripped 28.0 g (0.235 mol) of thionyl chloride was added, and the addition was completed in about 1 hour. After the dropwise addition was completed, the temperature was raised to 80 C for 2 hours, and the reaction was completed to obtain a 4-(trifluoromethyl)nicotinyl chloride solution.
  • 23
  • [ 6011-14-9 ]
  • [ 81565-19-7 ]
  • flonicamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In water; toluene; at 10 - 30℃; for 5h; In a 1000 ml four-necked flask equipped with a thermometer and a dropping funnel, 33.3 g (0.314 mol) of sodium carbonate and 133.2 g of tap water were charged, and after stirring for 10 minutes, 120 ml of toluene was added, and aminoacetonitrile hydrochloride was 21.79 g (0.235). Mol), then the temperature is lowered to 10 C under stirring, and the dropwise addition of <strong>[81565-19-7]4-(trifluoromethyl)nicotinyl chloride</strong> solution is started. The addition is completed in about 3 hours, the temperature is maintained at 10-15 C, and the addition is completed. After incubation at 30 C for 2 hours, the reaction was completed, filtered, and the product was washed with 30 ml of water to obtain a white solid product, N-cyanomethyl-4-(trifluoromethyl)nicotinamide.The purity was 99.8%, and the yield was 93.2% based on 4-(trifluoromethyl)nicotinic acid.
 

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Technical Information

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