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Chemical Structure| 144261-13-2 Chemical Structure| 144261-13-2

Structure of 144261-13-2

Chemical Structure| 144261-13-2

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Product Details of [ 144261-13-2 ]

CAS No. :144261-13-2
Formula : C15H20F2
M.W : 238.32
SMILES Code : CCC[C@H]1CC[C@H](C2=CC(F)=CC(F)=C2)CC1
MDL No. :MFCD09750933
InChI Key :GHOUEKQRKXYGHJ-UHFFFAOYSA-N
Pubchem ID :18469434

Safety of [ 144261-13-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 144261-13-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.6
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 67.67
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.53
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

5.99
Log Po/w (WLOGP)?

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

5.88
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.

5.32
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

5.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.19

Water Solubility

Log S (ESOL):?

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

-5.15
Solubility 0.00167 mg/ml ; 0.00000701 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.77
Solubility 0.000408 mg/ml ; 0.00000171 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-5.37
Solubility 0.00103 mg/ml ; 0.00000432 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
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

Yes
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.

-3.5 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

1.0
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<2.0
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)

2.8

Application In Synthesis of [ 144261-13-2 ]

* 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.

  • Upstream synthesis route of [ 144261-13-2 ]

[ 144261-13-2 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 148150-92-9 ]
  • [ 144261-13-2 ]
YieldReaction ConditionsOperation in experiment
58.05 g
Stage #1: With toluene-4-sulfonic acid In toluene for 2 h; Inert atmosphere; Reflux
Stage #2: With 5%-palladium/activated carbon; hydrogen In ethyl acetate for 6 h; Inert atmosphere
Stage #3: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 4 h; Inert atmosphere
10106] (3-2) In a nitrogen atmosphere, 132 g of crude 1-(1 - hydroxy-4-propylcyclohexyl)-3,5-difluorobenzene and 2.99 g of p-toluenesulfonic monohydrate were dissolved in 250 mE of toluene, and the resultant solution was stirred for 2 hours under reflux while the produced water was removed. Afier the solution was allowed to cool to room temperature, an organic layer was washed with a saturated aqueous sodium bicarbonate solution and saturated brine, and dried by adding sodium sulfate, and then the solvent was distilled off underreduced pressure. Then, the whole amount of the resultantresidue was dissolved in 280 mE of ethyl acetate, and 7.1 g ofpalladium 5percent/carbon was added to the solution, followed bystirring in a hydrogen atmosphere at 5 Mpa for 6 hours. After the palladium catalyst was filtered off, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography. Then, the whole amount of the resultant product and 3.39 g of tertiary butoxypotassium were dissolved in 350 mE of DMF, followed by stirring at room temperature for 4 hours. Then, water and hexane were added to separate an organic layet Further, an aqueous layer was subjected to extraction with hexane, and the hexane extract was combined with the organic layer and washed with saturated brine. The resultant mixture was dried by adding sodium sulfate, the solvent was distilled off, and distillation under reduced pressure (206 Pa, b. p.=llO° C. to 112° C.) yielded 58.05 g of 1-(trans-4-propylcyclohexyl)-3, 5 -difluorobenzene.
58.05 g
Stage #1: With toluene-4-sulfonic acid In toluene for 2 h; Inert atmosphere; Reflux
Stage #2: With 5%-palladium/activated carbon; hydrogen In ethyl acetate for 6 h;
In a nitrogen atmosphere, 132 g of the crude 1- (1-hydroxy-4-propylcyclohexyl) -3,5-difluorobenzene obtained in (1-1) and 132 g of p-toluenesulfonic acid monohydrate 2.99 g was dissolved in 250 mL of toluene, and the mixture was stirred under reflux for 2 hours while removing water produced. After leaving to be cooled to room temperature, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, the obtained total amount was dissolved in 280 mL of ethyl acetate, 7percent of 5percent palladium / carbon was added, and the mixture was stirred at 5 MPa in a hydrogen atmosphere for 6 hours. After separating the palladium catalyst by filtration, the solvent was distilled off under reduced pressure and purified by silica gel column chromatography. Subsequently, the whole amount obtained and 3.39 g of tertiary butoxypotassium were dissolved in 350 mL of DMF and stirred at room temperature for 4 hours. Water and hexane were added and the layers were separated, and the organic layer was separated. The aqueous layer was extracted with hexane,The organic layers were combined and washed with saturated brine. Sodium sulfate was added and dried, the solvent was distilled off, and distillation under reduced pressure (206 Pa, b.p. = 110 to 112 ° C.) gave 1- (trans-4-propylcyclohexyl) -3,5-difluorobenzene 58.05 g was obtained.
References: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 364, p. 899 - 910.
[2] Patent: US2014/275577, 2014, A1, . Location in patent: Paragraph 0104; 0106.
[3] Patent: JP6085912, 2017, B2, . Location in patent: Paragraph 0063; 0064; 0066.
  • 2
  • [ 173306-02-0 ]
  • [ 144261-13-2 ]
References: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 1995, vol. 260, # pt 1, p. 93 - 105.
  • 3
  • [ 461-96-1 ]
  • [ 144261-13-2 ]
References: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 364, p. 899 - 910.
[2] Patent: JP6085912, 2017, B2, .
  • 4
  • [ 40649-36-3 ]
  • [ 144261-13-2 ]
References: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 364, p. 899 - 910.
[2] Patent: JP6085912, 2017, B2, .
  • 5
  • [ 148151-00-2 ]
  • [ 144261-13-2 ]
References: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 364, p. 899 - 910.
  • 6
  • [ 461-96-1 ]
  • [ 40649-36-3 ]
  • [ 144261-13-2 ]
References: [1] Patent: US2014/275577, 2014, A1, .
 

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