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Chemical Structure| 889865-38-7 Chemical Structure| 889865-38-7

Structure of 889865-38-7

Chemical Structure| 889865-38-7

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Product Details of [ 889865-38-7 ]

CAS No. :889865-38-7
Formula : C17H25BO4
M.W : 304.19
SMILES Code : CC1(C)OB(OC1(C)C)C1=CC=C(OC2CCCCO2)C=C1
MDL No. :MFCD16294419
InChI Key :ZIKLUMIQYINQLY-UHFFFAOYSA-N
Pubchem ID :58005653

Safety of [ 889865-38-7 ]

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

Computational Chemistry of [ 889865-38-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 6
Fraction Csp3 0.65
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 87.61
TPSA ?

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

36.92 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

3.74
Log Po/w (WLOGP)?

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

2.89
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.

1.97
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

2.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.21

Water Solubility

Log S (ESOL):?

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

-4.09
Solubility 0.025 mg/ml ; 0.000082 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.

-4.21
Solubility 0.0189 mg/ml ; 0.000062 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

-4.62
Solubility 0.00726 mg/ml ; 0.0000239 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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.5 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

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<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)

4.05

Application In Synthesis of [ 889865-38-7 ]

* 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 [ 889865-38-7 ]

[ 889865-38-7 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 36603-49-3 ]
  • [ 61676-62-8 ]
  • [ 889865-38-7 ]
YieldReaction ConditionsOperation in experiment
74%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h;
Stage #2: at -78 - 20℃; for 2.5 h;
Compound 11 (2-(4-bromophenoxy)tetrahydro-2H-pyran,10.7 g, 41.6 mmol) dissolved in THF (220.0 mL, 20 mL/g)After cooling to -78 ° C, slowly dropping n-butyl lithium(21.6 mL, 54.1 mmol, 2.5 M hexane solution),It was stirred at -78 ° C for 30 minutes.Slowly drip 2-isopropoxy-4,4,5,5-tetramethyl- in the mixed solution1,3,2-dioxaborolane 12 (2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 11.0 mL, 54.1 mmol).Then, the obtained reactant is heated from -78 ° C to room temperature.And further stirred for 2.5 hours.The reaction was quenched by the addition of a saturated ammonium chloride solution.The organic layer is separated by an organic solvent,The organic layer was dried over anhydrous sodium sulfate and filtered and evaporated.The residue was concentrated to silica gel column chromatography (hexane:EtOAc = 10:1)Purification was carried out to give a white solid compound 13 (9.4 g, yield: 74percent).
References: [1] Patent: CN109206387, 2019, A, . Location in patent: Paragraph 0142; 0143; 0148; 0149; 0150.
  • 2
  • [ 110-87-2 ]
  • [ 540-38-5 ]
  • [ 73183-34-3 ]
  • [ 889865-38-7 ]
YieldReaction ConditionsOperation in experiment
76% With potassium acetate; dimethyl sulfoxide In water 1)
Production of 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1-(2-tetrahydropyranyloxy)benzene:
Potassium acetate (5.8 g, 59.2 mmol) and bis(diphenylphosphino)ferrocene palladium(II) dichloride-dichloromethane (806 mg, 0.99 mmol) were added to a dimethyl sulfoxide (70 mL) solution of 4-iodophenol tetrahydropyranyl ether (6.0 g, 19.7 mmol) readily preparable from 4-iodophenol and dihydropyran, and bis(pinacolato)diboron (6.01 g, 23.7 mmol), and stirred in a nitrogen atmosphere at 75°C for 1 hour.
The reaction mixture was cooled to room temperature, water was added to it, and extracted with ethyl acetate.
The organic layer was washed with water and saturated brine, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was purified through silica gel column chromatography (C-300, hexane/ethyl acetate = 8/1) to obtain the entitled compound (4.54 g, 76 percent).
References: [1] Patent: EP1820797, 2007, A1, .
  • 3
  • [ 4203-50-3 ]
  • [ 73183-34-3 ]
  • [ 889865-38-7 ]
References: [1] Patent: WO2006/59778, 2006, A1, . Location in patent: Page/Page column 55.
  • 4
  • [ 110-87-2 ]
  • [ 889865-38-7 ]
References: [1] Patent: CN109206387, 2019, A, .
 

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