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Chemical Structure| 1486-53-9 Chemical Structure| 1486-53-9

Structure of 1486-53-9

Chemical Structure| 1486-53-9

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Product Details of [ 1486-53-9 ]

CAS No. :1486-53-9
Formula : C15H14O4
M.W : 258.27
SMILES Code : O=C(O)C1=CC=C(OCC2=CC=CC=C2)C(OC)=C1
MDL No. :MFCD00183281
InChI Key :JGMBQAGNZLBZCE-UHFFFAOYSA-N
Pubchem ID :226335

Safety of [ 1486-53-9 ]

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

Computational Chemistry of [ 1486-53-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 12
Fraction Csp3 0.13
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 70.87
TPSA ?

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

55.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.33
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

3.1
Log Po/w (WLOGP)?

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

2.82
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.

2.47
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

2.71

Water Solubility

Log S (ESOL):?

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

-3.53
Solubility 0.0759 mg/ml ; 0.000294 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.

-3.94
Solubility 0.0297 mg/ml ; 0.000115 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

-4.57
Solubility 0.00703 mg/ml ; 0.0000272 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

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

Yes
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.

-5.67 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

0.0
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<0.0
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)

2.12

Application In Synthesis of [ 1486-53-9 ]

* 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 [ 1486-53-9 ]

[ 1486-53-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1486-53-9 ]
  • [ 74-88-4 ]
  • [ 56441-97-5 ]
YieldReaction ConditionsOperation in experiment
90% With potassium carbonate; In acetone; for 16.0h;Heating / reflux; Preparation of 4-benzyloxy-3-methoxy-methylbenzoate 2.84 g of 4-benzyloxy-3-methoxy-benzoic acid was combined with 3.04 g of potassium carbonate and 1.03 mL of iodomethane in 100 mL of acetone. The mixture was refluxed for 16 hours, cooled to room temperature and diluted with dichloromethane. The slurry was filtered and washed with dichloromethane and the filtrate concentrated to dryness. The solids were redissolved in dichloromethane, washed twice with water, dried over sodium sulfate and filtered. The filtrate was concentrated to a clear, colorless oil which was triturated with methanol to give a white solid in 90% yield (2.7 grams). Proton
  • 3
  • [ 1486-53-9 ]
  • [ 491-71-4 ]
  • 4
  • [ 56441-97-5 ]
  • [ 1486-53-9 ]
YieldReaction ConditionsOperation in experiment
74% With sodium hydroxide; In methanol; for 4.0h;Heating / reflux; E) 4-Benzyloxy-3-methoxy benzoic acid; A solution of sodium hydroxide (2.0 g) in methanol (50 ml) was added to a solution of 4-benzyloxy-3-methoxy benzoic acid methyl ester (4.64 g) in methanol (50 ml) and refluxed for 4 hrs. After removal of methanol under reduced pressure the residue was dissolved in water (150 ml) and washed with ethyl acetate (2 x 50 ml). The aqueous layer was acidified with 2N hydrochloric acid to pH 2. The precipitated product was collected by filtration which on drying under vacuum provided 4.17 g of 4-benzyloxy- 3-methoxy benzoic acid. (Yield = 74%) 'H NMR CDCl3 7.7 (1H, d, J = 8Hz) 7.63 (1H, s) 7.3-7.5 (5H, m) 6.92 (1H, d, J 8Hz) 5.25 (2H, s) 3.98 (3H, s)
(1) Benzyl bromide (3.59 ml) and potassium carbonate (5.69 g) were added to an acetone (50 ml) solution of methyl 4-hydroxy-3-methoxybenzoate (5.00 g), and heated at reflux for 4 hours. After removing solid matter by filtration and concentrating the filtrate under reduced pressure, the residue was dissolved in ethyl acetate, and washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine. The organic layer was dried over MgSO4, and the solvent was evaporated under reduced pressure, thereby giving 7.47 g of <strong>[56441-97-5]methyl 4-benzyloxy-3-methoxybenzoate</strong>.(2) An aqueous 2 M sodium hydroxide solution (13.72 ml) was added to an ethanol (15 ml) solution of the above-obtained 4-benzyloxy compound (7.47 g), and heated at reflux for 2 hours. After evaporating the solvent under reduced pressure, 2M hydrochloric acid was added, and the thus-precipitated crystals were filtered, thereby giving 7.00 g of the desired compound.
  • 5
  • [ 1486-53-9 ]
  • [ 56441-97-5 ]
YieldReaction ConditionsOperation in experiment
80% With sulfuric acid; In methanol; for 10.0h;Reflux; A catalytic amount of concentrated H2SO4 was added to a solution of compound 3 (5.4g, 20.9mmol) in 50mL of methanol and the mixture was refluxed for 10h. It was allowed to cool. The product crystallization from solution gave pure 4 (4.5g) as a white solid with a yield of 80%. Mp: 70-72C; 1H NMR (CDCl3, 300MHz): delta (ppm) 3.90 (s, 3H), 3.95 (s, 1H), 5.23 (s, 2H), 7.32-7.57 (m, 5H), 7.58 (s, 1H), 7.60-7.61 (d, J=2.0Hz, 1H), 7.63-7.64 (d, J=1.8Hz, 1H).
  • 6
  • [ 67-56-1 ]
  • [ 1486-53-9 ]
  • [ 56441-97-5 ]
YieldReaction ConditionsOperation in experiment
80% With sulfuric acid; In methanol; for 10.0h;Reflux; A solution of 3-methoxy-4-benzyloxybenzoic acid (20.9 mmol, 5.4 g) in 50 ml of methanol was added to a 250 ml reaction flask, and 1 ml of concentrated sulfuric acid was slowly added dropwise with stirring. The mixture was heated under reflux for 10 hours.Concentrated and crystallized from methanol, filtration, the filter cake washed with a small amount of methanol, and dried to give a white solid 4.5g, 3-methoxy-4-benzyloxy-benzoic acid methyl ester Yield% 80,
 

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