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Chemical Structure| 25173-76-6

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Product Details of [ 25173-76-6 ]

CAS No. :25173-76-6
Formula : C11H14O2
M.W : 178.23
SMILES Code : O=C(O)CCC1=CC=C(C)C(C)=C1
MDL No. :MFCD03425686
Boiling Point : No data available
InChI Key :FHEOAGCWJWUKJJ-UHFFFAOYSA-N
Pubchem ID :3870218

Safety of [ 25173-76-6 ]

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

Computational Chemistry of [ 25173-76-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 52.73
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.

1.89
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

3.46
Log Po/w (WLOGP)?

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

2.32
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.

2.58
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

2.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.62

Water Solubility

Log S (ESOL):?

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

-3.27
Solubility 0.0961 mg/ml ; 0.000539 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.

-3.92
Solubility 0.0212 mg/ml ; 0.000119 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

-3.35
Solubility 0.0791 mg/ml ; 0.000444 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.

-4.93 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.

0.56

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)

1.13

Application In Synthesis of [ 25173-76-6 ]

* 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.

  • Upstream synthesis route of [ 25173-76-6 ]

[ 25173-76-6 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 147219-20-3 ]
  • [ 25173-76-6 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogen In methanol at 20℃; for 4 h; A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before methanol (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3- (3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation.
98% With hydrogen In methanol at 20℃; for 4 h; A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before MeOH (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3-(3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation.
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 3, p. 677 - 682.
[2] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200.
[3] Patent: WO2008/26149, 2008, A1, . Location in patent: Page/Page column 22.
[4] Patent: WO2008/78291, 2008, A1, . Location in patent: Page/Page column 39.
[5] Collection of Czechoslovak Chemical Communications, 1967, vol. 32, p. 4082 - 4098.
  • 2
  • [ 102-46-5 ]
  • [ 105-53-3 ]
  • [ 25173-76-6 ]
YieldReaction ConditionsOperation in experiment
55% With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water Step 1)
Synthesis of 3-(3,4-dimethylphenyl)propionic acid
To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metallic sodium.
The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto.
This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure.
The residue was dissolved in ethyl ether and the solution was washed with water.
After further concentration under a reduced pressure, the organic phase was combined with 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours.
The mixture was concentrated under a reduced pressure to about one half volume; then 200 ml of 98percent sulfuric acid was added slowly thereto.
The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl acetate.
The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.1 g of the title compound as a white solid(yield: 55percent).
m.p.: 82° C.
1 H-NMR(300 MHz, CDCl3) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93-7.70(m, 3H, ArH)
55% With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid
To a solution of 70.0ml of diethyl malonate dissolved in 400ml of dry ethanol was added 10.0g of metallic sodium.
The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto.
This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure.
The residue was dissolved in ethyl ether and the solution was washed with water.
After further concentration under a reduced pressure, the organic phase was combined with 500ml of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours.
The mixture was concentrated under a reduced pressure to about one half volume; then 200ml of 98percent sulfuric acid was added slowly thereto.
The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300ml of ethyl acetate.
The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.lg of the title compound as a white solid(yield: 55percent).
m.p.: 82°C
1H NMR(300MHz, CDCl3) δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93-7.70(m, 3H, ArH)
References: [1] Patent: US5670546, 1997, A, .
[2] Patent: EP721939, 1996, A1, .
  • 3
  • [ 102-46-5 ]
  • [ 105-53-3 ]
  • [ 25173-76-6 ]
  • [ 142332-70-5 ]
YieldReaction ConditionsOperation in experiment
55% With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water PREPARATION EXAMPLE 1
Synthesis of 3-(3,4-dimethylphenyl)propylamine
To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metalic sodium.
The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto.
This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether.
This ethereal solution was washed with water.
To the residues obtained after a further concentration of the organic phase were added 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours.
This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200 ml of sulfuric acid was then slowly added thereto.
The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1 g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid (yield 55percent), having the characteristics of: m.p. 82° C.; NMR(CDCl3, 300 MHz) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93~7.70(m, 3H, ArH).
55% With potassium hydroxide; sulfuric acid In diethyl ether; ethanol Preparation Example 1:
Synthesis of 3-(3,4-dimethylphenyl)propylamine
To a solution of 70.0m of diethyl malonate dissolved in 400m of dry ethanol was added 10.0g of metalic sodium.
The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto.
This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether.
This ethereal solution was washed with water.
To the residues obtained after a further concentration of the organic phase were added 500m of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours.
This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200m of sulfuric acid was then slowly added thereto.
The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300m of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid(yield 55percent), having the characteristics of: m.p. 82°C; NMR(CDCl3, 300MHz)δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93~7.70(m, 3H, ArH).
References: [1] Patent: US5242944, 1993, A, .
[2] Patent: EP525360, 1993, A2, .
  • 4
  • [ 7440-32-6 ]
  • [ 60521-25-7 ]
  • [ 25173-76-6 ]
References: [1] Patent: EP1157047, 2003, B1, .
  • 5
  • [ 5973-71-7 ]
  • [ 25173-76-6 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 3, p. 677 - 682.
[2] Collection of Czechoslovak Chemical Communications, 1967, vol. 32, p. 4082 - 4098.
  • 6
  • [ 6966-10-5 ]
  • [ 25173-76-6 ]
References: [1] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200.
  • 7
  • [ 38404-42-1 ]
  • [ 25173-76-6 ]
References: [1] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200.
  • 8
  • [ 619-04-5 ]
  • [ 25173-76-6 ]
References: [1] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200.
 

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