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Chemical Structure| 480425-35-2 Chemical Structure| 480425-35-2

Structure of 480425-35-2

Chemical Structure| 480425-35-2

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Product Details of [ 480425-35-2 ]

CAS No. :480425-35-2
Formula : C14H19BO4
M.W : 262.11
SMILES Code : COC(=O)C1=CC=CC(=C1)B1OC(C)(C)C(C)(C)O1
MDL No. :MFCD03789258
InChI Key :JBJGSVBGUBATNH-UHFFFAOYSA-N
Pubchem ID :2734651

Safety of [ 480425-35-2 ]

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

Computational Chemistry of [ 480425-35-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 74.2
TPSA ?

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

44.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.76
Log Po/w (WLOGP)?

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

1.77
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.

1.54
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

1.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.57

Water Solubility

Log S (ESOL):?

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

-3.24
Solubility 0.151 mg/ml ; 0.000576 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.

-3.36
Solubility 0.116 mg/ml ; 0.000441 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

-4.08
Solubility 0.022 mg/ml ; 0.0000839 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

Yes
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.

-5.94 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.

0.55

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<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)

3.01

Application In Synthesis of [ 480425-35-2 ]

* 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.

  • Downstream synthetic route of [ 480425-35-2 ]

[ 480425-35-2 ] Synthesis Path-Downstream   1~3

  • 2
  • [ 618-89-3 ]
  • [ 73183-34-3 ]
  • [ 480425-35-2 ]
YieldReaction ConditionsOperation in experiment
83% With meso-tetra(p-tolyl)porphinato-palladium(II); potassium acetate; In 1,4-dioxane; at 110℃; for 7h; General procedure: Aryl/heteroaryl bromide 1 (1 mmol), B2pin2(2), B2npg2(4) orBpin (6, 1.2 mmol), and dioxane (5 mL) are taken into a 25 mLround-bottomed flask. KOAc (2 mmol) was added and stirredthe resultant mixture at room temperature for 5 min, PdII-TpTP(0.15 mol%) was added, and the contents were refluxed on preheatedoil bath at 110 C under constant stirring in open-air.The reaction progress was ensured by TLC. After completion ofthe reaction, the mixture was cooled, dilute with water (20 mL)and extracted with tertbutylmethyl ether (3 × 10 mL). The combinedn-hexane layers were concentrated, and the crudeproduct obtained was purified by column chromatography (CC)on silica gel using a mixture of ethyl acetate and hexane (1:30)as eluent.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; for 2h;Reflux; Inert atmosphere; General procedure: A mixture of substituted 3-(or 4-) bromobenzamides or 3-bromobenzoate or N-(3-(or 4-)bromophenyl)acetamide 3, (0.5 mmol), bis(pinacolato)diboron (0.14 g, 0.55 mmol), potassium acetate (0.15 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol) and 1,4-dioxane (10 mL) was refluxed for 2 h under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a dark brown residue. To the residue was added intermediate 2 (0.4 mmol), sodium carbonate (0.16 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol), 1,2-dimethoxyethane (8 mL) and water (2 mL) and the mixture was refluxed for 2 h under nitrogen atmosphere. The mixture was evaporated under reduced pressure and purified by silica gel column chromatography using chloroform/methanol = 30: 1 as the eluent to afford the compounds T1-T6, T9-T10, T12 and T14-T21 as an off-white or a white solid.
  • 3
  • [ 480425-35-2 ]
  • [ 443776-76-9 ]
YieldReaction ConditionsOperation in experiment
Step 1(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol Procedure:To a suspension of LiAlH4 (100 mg, 2.63 mmol) in THF (30 mL) was added portion-wise at room temperature methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (200 mg, 0.76 mmol). The reaction mixture was stirred at room temperature for additional 3 h. H2O (3 mL) was added dropwise at 0 C. then the mixture was filtered and concentrated under reduced pressure to give crude (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (190 mg) which was used for next step without characterization or purification.
With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 3h; To a suspension of LiAlH4 (100 mg, 2.63 mmol) in THF (30 mL) was added portion-wise at room temperature methyl 3-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzoate (200 mg, 0.76 mmol).. The reaction mixture was stirred at room temperature for additional 3 h. H20 (3 mL) was added dropwise at 0C then the mixture was filtered and concentrated under reduced pressure to give crude (3-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2- yl)phenyl)methanol (190 mg) which was used for next step without characterization or purification.
 

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Technical Information

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