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Chemical Structure| 137756-89-9 Chemical Structure| 137756-89-9

Structure of 137756-89-9

Chemical Structure| 137756-89-9

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Product Details of [ 137756-89-9 ]

CAS No. :137756-89-9
Formula : C8H11BO3
M.W : 165.98
SMILES Code : OCCC1=CC=C(B(O)O)C=C1
MDL No. :MFCD03095135
InChI Key :KQXBZMDDTQEGMT-UHFFFAOYSA-N
Pubchem ID :10176286

Safety of [ 137756-89-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 137756-89-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 3.0
Molar Refractivity 47.2
TPSA ?

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

60.69 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

0.4
Log Po/w (WLOGP)?

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

-1.1
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.

0.06
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

-0.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.24

Water Solubility

Log S (ESOL):?

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

-1.29
Solubility 8.45 mg/ml ; 0.0509 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.24
Solubility 9.53 mg/ml ; 0.0574 mol/l
Class?

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

Very 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

-1.51
Solubility 5.07 mg/ml ; 0.0305 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

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

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.

-7.03 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

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<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)

1.51

Application In Synthesis of [ 137756-89-9 ]

* 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.

  • Upstream synthesis route of [ 137756-89-9 ]
  • Downstream synthetic route of [ 137756-89-9 ]

[ 137756-89-9 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 4654-39-1 ]
  • [ 137756-89-9 ]
YieldReaction ConditionsOperation in experiment
63%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.5 h;
Stage #2: With hydrogenchloride; Triisopropyl borate In tetrahydrofuran; hexane; water at -78 - 20℃; for 1 h;
To a stirred solution of 4-bromophenethylalcohol (5.00 g, 24.9 mmol) in THF (80 ml) was added a solution of 1.5M n-BuLi in hexane (39.8 ml, 59.7 mmol) at -78° C. over 30 min. After 1 hour, a solution of B(OiPr)3 (8.61 ml, 37.3 mmol) in THF (20 ml) was added slowly to the mixture at -78° C. The resultant mixture was warmed to room temperature, and treated with 2M HCl (100 ml) for 1 hour. This was extracted with CH2Cl2 and dried over MgSO4, then filtered. After evaporation in vacuo, the residue was purified by silica-gel column chromatography eluting with CH2Cl2/MeOH=20/1 to afford 2.61 g (63percent) of the title compound. [2789] 1H-NMR (CD3OD) δ: 7.64-7.48 (2H, m), 7.19-7.13 (2H, m), 3.70 (2H, t, J=7.2 Hz), 2.77 (2H, t, J=7.2 Hz) MS (ESI) m/z: 165 ([M-H]-)
63% With n-butyllithium; Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 1.5 h; To a stirred solution of 4-bromophenethylalcohol (5.00 g, 24.9 mmol) in tetrahydrofuran (80 mL) was added a solution of 1.5 M n-butyl lithium in hexane (39.8 mL, 59.7 mmol) at -78° C. over 30 min. After 1 h, a solution of triisopropyl borate (8.61 mL, 37.3 mmol) in tetrahydrofuran (20 mL) was added slowly to the mixture at -78° C. The resultant mixture was warmed to room temperature, and treated with 2 M HCl (100 mL) for 1 h. This mixture was extracted with dichloromethane and dried (MgSO4). After evaporation in vacuo, the residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (20:1) to afford 2.61 g (63percent) of the title compound as white solids
References: [1] Patent: US2003/236260, 2003, A1, . Location in patent: Page 114.
[2] Patent: US2004/19045, 2004, A1, . Location in patent: Page 52.
  • 2
  • [ 5419-55-6 ]
  • [ 4654-39-1 ]
  • [ 7732-18-5 ]
  • [ 137756-89-9 ]
YieldReaction ConditionsOperation in experiment
37%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 35℃; for 1.5 h;
Stage #2: at -78 - 35℃;
Stage #3: With ammonium chloride In tetrahydrofuran; hexane
(Step 1)
To a solution of 2-(4-bromophenyl)ethanol (3.00 g, 14.9 mmol) in THF (60 mL) was added 1.6 M butyllithium/hexane solution (23.3 mL, 37.3 mmol) at -78° C. and the mixture was stirred at -78° C. for 1 hr and then at room temperature for 30 min.
The reaction mixture was cooled again to -78° C. and triisopropylboric acid (7.02 g, 37.3 mmol) was added.
The mixture was gradually heated to room temperature.
Saturated aqueous ammonium chloride solution (150 mL) was added and the mixture was extracted with ethyl acetate.
The organic layer was washed with saturated brine, and dried over anhydrous-sodium sulfate.
The solvent was evaporated under reduced pressure, and the concentrated residue was purified by silica gel column chromatography (67-100percent ethyl acetate/hexane-9percent methanol/ethyl acetate) to give [4-(2-hydroxyethyl)phenyl]boronic acid as a colorless amorphous form (925 mg, 37percent).
References: [1] Patent: US2015/329556, 2015, A1, . Location in patent: Paragraph 1862-1863.
  • 3
  • [ 4654-39-1 ]
  • [ 137756-89-9 ]
YieldReaction ConditionsOperation in experiment
63% With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane Step. 4-(2-hydroxyethyl)phenylboronic acid
To a stirred solution of 4-bromophenethylalcohol (5.00 g, 24.9 mmol) in THF (80 ml) was added a solution of 1.5M n-BuLi in hexane (39.8 ml, 59.7 mmol) at -78° C. over 30 min.
After 1 hour, a solution of B(OiPr)3 (8.61 ml, 37.3 mmol) in THF (20 ml) was added slowly to the mixture at -78° C.
The resultant mixture was warmed to room temperature, and treated with 2M HCl (100 ml) for 1 hour.
This was extracted with CH2Cl2 and dried over MgSO4, then filtered.
After evaporation in vacuo, the residue was purified by silica-gel column chromatography eluding with CH2Cl2/MeOH=20/1 to afford 2.61 g (63percent) of the title compound.
1H-NMR (CD3OD) δ: 7.64-7.48 (2H, m), 7.19-7.13 (2H, m), 3.70 (2H, t, J=7.2 Hz), 2.77 (2H, t, J=7.2 Hz)
MS (ESI) m/z: 165 ([M-H]-)
References: [1] Patent: US2002/77329, 2002, A1, .
 

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