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Chemical Structure| 306761-54-6

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Product Details of [ 306761-54-6 ]

CAS No. :306761-54-6
Formula : C10H12F3N
M.W : 203.20
SMILES Code : CC(N)(C1=CC=C(C(F)(F)F)C=C1)C
MDL No. :MFCD09258816
InChI Key :BZZQAWGDEQZOOF-UHFFFAOYSA-N
Pubchem ID :22337579

Safety of [ 306761-54-6 ]

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

Computational Chemistry of [ 306761-54-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.4
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 48.61
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.28
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

2.39
Log Po/w (WLOGP)?

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

3.94
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.

3.19
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

2.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.93

Water Solubility

Log S (ESOL):?

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

-2.79
Solubility 0.329 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.

-2.58
Solubility 0.537 mg/ml ; 0.00264 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

-3.75
Solubility 0.0359 mg/ml ; 0.000177 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

Yes
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.

-5.84 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

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)

1.19

Application In Synthesis of [ 306761-54-6 ]

* 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 [ 306761-54-6 ]

[ 306761-54-6 ] Synthesis Path-Downstream   1~9

  • 1
  • N-(α,α-Dimethyl-p-trifluoromethylbenzyl)formamide [ No CAS ]
  • [ 306761-54-6 ]
  • 2
  • [ 455-18-5 ]
  • [ 75-16-1 ]
  • [ 306761-54-6 ]
YieldReaction ConditionsOperation in experiment
1.81 g Reference Example 27-3 2-[4-(Trifluoromethyl)phenyl]propane-2-amine To a solution of 4-(trifluoromethyl)benzonitrile (3.01 g) in diethyl ether (88.0 mL), methylmagnesium bromide (about 3.0 mol/L, solution in diethyl ether, 17.6mL) was added and the mixture was stirred at room temperature for 40 minutes. To the reaction mixture, tetraisopropyl orthotitanate (5.15 mL) was added slowly and thereafter the mixture was refluxed for 6 hours. After cooling the mixture to 0C, an aqueous solution of 20% sodium hydroxide was added and the mixture was stirred at room temperature for an hour. After phase separation, the aqueous layer was extracted with diethyl ether twice. The combined organic layers were passed through a phase separator and thereafter concentrated under reduced pressure. The resulting residue was dissolved in 5% hydrochloric acid and washed with diethyl ether twice. The aqueous layer was rendered basic with an aqueous solution of 20% sodium hydroxide and extracted with diethyl ether three times. The combined organic layers were washed with saturated brine and thereafter passed through a phase separator to be concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5-10:90) to give the titled compound as a yellow oil (1.81 g). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 6 H) 7.54 - 7.69 (m, 4 H). MS ESI/APCI Dual posi: 204[M+H]+.
  • 3
  • [ 2252-62-2 ]
  • [ 306761-54-6 ]
  • 4
  • [ 402-43-7 ]
  • [ 306761-54-6 ]
  • 5
  • [ 1120-71-4 ]
  • [ 306761-54-6 ]
  • 3-[2-(4-trifluoromethylphenyl)-2-propylamino]-1-propanesulfonic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% In toluene; acetonitrile; for 24h;Heating / reflux; Preparation of 3-[2-(4-trifluoromethylphenyl)-2-propylamino]-1-propanesulfonic acid A mixture of <strong>[306761-54-6]1-(4-trifluoromethylphenyl)-1-methylethylamine</strong> (8.30 mmol, 1.69 g), 1,3-propane sultone (8.5 mmol, 0.75 mL), MeCN (7 mL) and toluene (3 mL) was heated to reflux for 24 hours. After cooling to room temperature, the solid was collected by filtration, rinsed with ethanol (3*5 mL) and dried for 1 hour at 60 C. in a vacuum oven (2.47 g). The solid obtained was suspended in 95% ethanol (20 mL) and the mixture was heated to reflux for 1 hour. After cooling to room temperature, the solid was collected by filtration, rinsed with ethanol (2*5 mL) and dried for 2 hours at 60 C. in a vacuum oven. The desired material was obtained as a white solid (2.39 g, 89%). 1H NMR (300 MHz, DMSO-d6) δ 1.69 (s, 6H), 1.94 (qt, J=6.4 Hz, 2H), 2.60 (t, J=6.4 Hz, 2H), 2.79 (br s, 2H), (q, J=8.5 Hz, 4H), 9.32 (br s, 2H); 13C (75 MHz, DMSO-d6) δ 22.25, 25.15, 41.97, 49.26, 59.93, 123.70 (q, J=271 Hz), 125.52 (d, J=3.5 Hz), 126.89, 128.71 (q, J=31.9 Hz)143.84; 19F (282 MHz, DMSO-d6) -61.87 (s); ES-MS 324 (M-1).
  • 6
  • [ 306761-54-6 ]
  • [ 140-88-5 ]
  • ethyl N-{2-[4-(trifluoromethyl)phenyl]propan-2-yl}-β-alaninate [ No CAS ]
YieldReaction ConditionsOperation in experiment
957 mg In methanol; water; at 90℃; for 1h;Microwave irradiation; Reference Example B-1 Ethyl N-{2-[4-(trifluoromethyl)phenyl]propan-2-yl}-β-alaninate To a mixture of the compound (1.11g) obtained in Reference Example 27-3, methanol (6.00 mL) and water (3.00 mL), ethyl acrylate (0.594 mL) was added and the resulting mixture was stirred at 90C for an hour under irradiation with microwaves. After being cooled to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate three times. The combined organic layers were washed with saturated brine and thereafter passed through a phase separator for concentrating under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5-10:90) to give the titled compound as a pale yellow oil (957 mg). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (t, J=7.1 Hz, 3 H) 1.47 (s, 6 H) 2.39-2.49 (m, 2 H) 2.53 - 2.61 (m, 2 H) 4.14 (q, J=7.1 Hz, 2 H) 7.58 (s, 4 H). MS ESI/APCI Dual posi: 304[M+H]+.
  • 7
  • [ 98141-42-5 ]
  • [ 306761-54-6 ]
  • 6-chloro-1-methyl-N-{1-methyl-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
  • 8
  • [ 455-18-5 ]
  • [ 917-54-4 ]
  • [ 306761-54-6 ]
YieldReaction ConditionsOperation in experiment
Step A: Anhydrous CeCl3 (0.84 g, 3.4 mmol) was stirred in dry THF (10 mL), at room temperature, under a N2 atmosphere for 2 h. Then, the solution was cooled at -78 C, followed by dropwise addition of MeLi (2.2 mL, 3.4 mmol, 1.6 M), and allowed to stir for 30 min at -78 C. Then, a solution of 4-methoxybenzonitrile (0.15 g, 1.1 mmol) in dry THF (5 mL) was added dropwise to the above solution. The crude reaction was stirred at room temperature overnight, quenched by adding 1.5 mL of concentrated NH4OH, and allowed to stir for 1 h at room temperature. The organic layer was filtered, dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was used for next reaction without further purification.
  • 9
  • [ 25084-14-4 ]
  • [ 306761-54-6 ]
  • 5-nitro-N-(2-(4-(trifluoromethyl)phenyl)propan-2-yl)furan-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; General procedure: Step B The crude from above (0.16 g, 0.97 mmol) was dissolved in dry DCM (5 mL) and a solution of 5-nitro-2-furoyl chloride (0.17 g, 0.97 mmol) in dry DCM (5 mL) was added dropwise, followed by dropwise addition of Et3N (0.27 mL, 1.9 mmol) at room temperature. The crude reaction was stirred at room temperature until reaction completion, diluted with DCM (10 mL), and washed with saturated aqueous brine solution (15 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Product was purified by column chromatography (95% DCM: 5% MeOH).
 

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