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Structure of 447-61-0

Chemical Structure| 447-61-0

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Product Details of [ 447-61-0 ]

CAS No. :447-61-0
Formula : C8H5F3O
M.W : 174.12
SMILES Code : C1=CC=CC(=C1C=O)C(F)(F)F
MDL No. :MFCD00003337
InChI Key :ZDVRPKUWYQVVDX-UHFFFAOYSA-N
Pubchem ID :123067

Safety of [ 447-61-0 ]

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

Computational Chemistry of [ 447-61-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 36.83
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.67
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

2.78
Log Po/w (WLOGP)?

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

3.67
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.

2.52
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

2.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.72

Water Solubility

Log S (ESOL):?

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

-2.91
Solubility 0.215 mg/ml ; 0.00123 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.

-2.79
Solubility 0.279 mg/ml ; 0.00161 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

-3.23
Solubility 0.103 mg/ml ; 0.000592 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.

-5.39 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

1.0 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)

1.1

Application In Synthesis of [ 447-61-0 ]

* 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 [ 447-61-0 ]

[ 447-61-0 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 447-61-0 ]
  • [ 75-16-1 ]
  • [ 79756-81-3 ]
  • 3
  • [ 13623-11-5 ]
  • [ 447-61-0 ]
  • 2-[2-hydroxy-2-(2-trifluoromethylphenyl)ethyl]-4,5-dimethyl-1,3-thiazole [ No CAS ]
  • 4
  • [ 80-65-9 ]
  • [ 447-61-0 ]
  • 3-[1-(2-Trifluoromethyl-phenyl)-meth-(E)-ylidene]-amino}-oxazolidin-2-one [ No CAS ]
  • 5
  • [ 447-61-0 ]
  • [ 1193-24-4 ]
  • [ 109-77-3 ]
  • 7-amino-4-oxo-5-(2-trifluoromethyl-phenyl)-3,5-dihydro-4<i>H</i>-pyrano[2,3-<i>d</i>]pyrimidine-6-carbonitrile [ No CAS ]
  • 6
  • [ 447-61-0 ]
  • [ 79286-79-6 ]
  • [ 820985-21-5 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; 3 (S)-Pyrrolidin-3-amine (0.45g, 5.2mmol) and trifluoromethylbenzaldehyde (0.87g, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243).
With toluene-4-sulfonic acid; toluene; for 24h;Heating / reflux; 3 (S)-PYRROLIDIN-3-AMINE (0.45g, 5.2mmol) and trifluoromethylbenzaldehyde (0. 87G, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243).
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; 3 (S)-PYRROLIDIN-3-AMINE (0.45g, 5.2mmol) and TRIFLUOROMETHYLBENZALDEHYDE (0.87g, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243).
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; 3 (S)-Pyrrolidin-3-amine (0.45g, 5. 2mmol) and trifluoromethylbenzaldehyde (0.87g, 5. 0mmol), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243).

  • 7
  • [ 447-61-0 ]
  • [ 79286-79-6 ]
  • [ 820985-23-7 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; A mixture of 3 (S)-pyrrolidin-3-amine (4g, 46. 5mmol), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5mmol), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245.
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; A mixture of 3 (S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150ML) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245.
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; A mixture of 3(S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245.
With hydrogen;palladium on activated carbon; In ethanol; under 3102.97 Torr; for 3h; A mixture of 3(S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245.

  • 8
  • [ 20101-92-2 ]
  • [ 447-61-0 ]
  • [ 1407496-53-0 ]
  • 9
  • [ 5654-97-7 ]
  • [ 447-61-0 ]
  • C15H9F3N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium ethanolate; In ethanol; at 20℃; General procedure: Various aldehydes (1.0 equiv) were added to stirred solutions of indolin-2-one, 5-chloroindolin-2-one or <strong>[5654-97-7]7-azaoxindole</strong> (1.0equiv) in absolute ethanol. After stirring at room temperature for 5 min NaOEt/EtOH (0.5 mL) was added and the mixture was then stirred at room temperature overnight. The solvent was then removed under vacuum. The residue was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum. The solid part was purified by chromatography over silica gel using ethyl acetate/petroleum ether as the eluent to afford desired compounds 1a-1g, 2a, 3a.
  • 10
  • [ 447-61-0 ]
  • [ 131674-40-3 ]
  • (E)-1-(2-methoxypyridin-3-yl)-3-(2-(trifluoromethyl)-phenyl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% General procedure: A solution of lithium hydroxide (0.8 mg, 0.03 mmol) and 2'-methoxyacetophenone (26 mg, 0.157 mmol) in absolute methanol (1.5 mL) was stirred at room temperature for 15 min. To the resulting mixture was added a solution of 2-(trifluoromethyl)-3-pyridinecarboxaldehyde (6a, 28 mg, 0.16 mmol) in absolute methanol (15 mL). The reaction was stirred overnight at room temperature (approx. 18 h). The reaction was then concentrated on a rotary evaporator and the resulting oily residue purified by chromatography on silica gel using a gradient of 0-100% ethyl acetate in hexane to provide the desired product (17 mg, 35%) as a light yellow waxy solid. Prepared using the general method from lithium hydroxide (1 mg, 0.04 mmol), 2-(trifluoromethyl)benzaldehyde (34 mg, 0.2 mmol) and <strong>[131674-40-3]1-(2-methoxypyridin-3-yl)ethanone</strong> (7d, 29 mg, 0.19 mmol) in absolute methanol (final reaction volume = 1.5 mL). The reaction mixture was purified by chromatography on silica gel (40% ethyl acetate in hexane) to give the desired product as a yellow solid (29 mg, 49%). 1H NMR (CDCl3) delta 8.36 (dd, J = 4.8, 2.0 Hz, 1H), 8.08 (dd, J = 7.4, 2.0 Hz, 1H), 8.05 (dd, J = 15.6, 2.2 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 15.7 Hz, 1H), 7.05 (dd, J = 7.4, 4.8 Hz, 1H), 4.09 (s, 3H). 13C NMR (CDCl3) delta 189.3, 160.6, 149.5, 138.9, 137.9, 135.9, 131.0, 130.1, 129.8, 128.6, 126.9, 125.2, 124.5, 121.2, 116.1, 52.8. HRMS (FAB): calcd C16H12F3NO2 + H = 308.0898, found 308.0874.
  • 11
  • [ 447-61-0 ]
  • [ 13338-63-1 ]
  • (Z)-2-(3,4,5-trimethoxyphenyl)-3-(2-trifluoromethylphenyl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
40.8% With sodium methylate; In methanol; at 60℃; Using the method of synthesizing an intermediate similar to that of Example 1,Take 0.01 mol of <strong>[13338-63-1]3,4,5-trimethoxyphenylacetonitrile</strong> (5), 0.01 mol of 2-trifluoromethylbromobenzaldehyde and 20 mL of methanol into a 50 mL three-necked flask.Stirring to 60 C, adding 0.005 mol of sodium methoxide, constant temperature reaction 4-6 h,TLC scanning and detection, after the reaction is completed, it is cooled to room temperature, filtered, washed with water, dried, and recrystallized from methanol to obtain a pale yellow solid. Yield: 40.8%,
 

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