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Structure of 908350-80-1

Chemical Structure| 908350-80-1

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Product Details of [ 908350-80-1 ]

CAS No. :908350-80-1
Formula : C17H20BNO2
M.W : 281.16
SMILES Code : CC1(OB(C2=CC=C(C3=NC=CC=C3)C=C2)OC1(C)C)C
MDL No. :MFCD11973624
InChI Key :CMGIUUPUDMXXLT-UHFFFAOYSA-N
Pubchem ID :53482118

Safety of [ 908350-80-1 ]

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

Computational Chemistry of [ 908350-80-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 12
Fraction Csp3 0.35
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 86.15
TPSA ?

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

31.35 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

3.5
Log Po/w (WLOGP)?

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

3.05
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.

1.89
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

2.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.27

Water Solubility

Log S (ESOL):?

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

-4.08
Solubility 0.0234 mg/ml ; 0.0000834 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.

-3.84
Solubility 0.0405 mg/ml ; 0.000144 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

-6.14
Solubility 0.000205 mg/ml ; 0.000000728 mol/l
Class?

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

Poorly 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

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

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.

-5.53 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)

3.02

Application In Synthesis of [ 908350-80-1 ]

* 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 [ 908350-80-1 ]

[ 908350-80-1 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 61676-62-8 ]
  • [ 908350-80-1 ]
YieldReaction ConditionsOperation in experiment
39%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h;
To a solution of 2-(4'-bromophenyl)pyridine (0.468 g, 2 mmol). in anhydrous THF (10 ml) was added dropwse n-BuL (3 ml, 3.6 mmol) at -78"C The reaction was stirred 1 h, then 2-isopropoxy-4,4,5>5-tetramethyl-l,3,2-dioxaborolane (0.52 ml, 2.5 mmol) was added. The mixture was stirred overnight. Then Hie reaction was quenched with water and extracted with dchloromethane (30 ml) 3 times. The organic layer was -washed with brine and dried over MgSO4 and concentrated in vacuo. After column chromatography (silica gel, ethyl acetate: hexane = 1: 20) to give product 0.22 g (39percent).
References: [1] Patent: WO2006/93466, 2006, A1, . Location in patent: Page/Page column 40.
  • 2
  • [ 63996-36-1 ]
  • [ 73183-34-3 ]
  • [ 908350-80-1 ]
YieldReaction ConditionsOperation in experiment
82% With potassium acetate; tricyclohexylphosphine In 1,4-dioxane for 20 h; Inert atmosphere; Reflux 1.
Preparation of 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)pyridine
0.39 g (0.4 mmol) of Pd(dba)3 and 0.28 g (1 mmol) of tricyclohexylphosphine are suspended in 10 ml of dry dioxane under a nitrogen atmosphere.
The resulting mixture is stirred at room temperature for 30 minutes.
Subsequently, 5.3 g (15 mmol) of bis(pinacolato)diboron, 2.1 g (21 mmol) of KOAc and 3.3 g (14 mmol) of 2-(4-bromophenyl)pyridine are added gradually.
The reaction mixture is boiled under reflux for 20 hours, cooled and treated with 10 ml of water at room temperature.
The product is extracted with dichloromethane.
The solvent is removed under reduced pressure and the resulting crude product is purified by means of a short silica gel column.
After purification by means of the silica gel column (dichloromethane/hexane, 3:1), 82percent of the desired product is obtained.
1H NMR(CDCl3): δ=1.37(s,12H), 7.22-7.26(m, 1H), 7.72-7.80(m, 2H), 7.92(J=8.4 Hz, 2H), 8.02(J=8.2Hz, 2H), 8.71(J=4.9 Hz, 1H).
11.2 g for 2 h; Inert atmosphere; Reflux First, a solution was added cyclopentyl methyl ether (CPME) in (64 ml) 2-(4- bromophenyl) pyridine (15 g) and bis (pinacolato) diboron (19.5 g), under a nitrogen atmosphere, palladium acetate (Pd ( OAc) 2) (0.4g), triphenylphosphine (PPh3) (1.5g) and potassium acetate (AcOK) (18.9g) was added with stirring at room temperature. After stirring for 2 hours at reflux temperature, the reaction mixture was cooled to room temperature, was added with ethylenediaminetetraacetic acid (EDTA) solution (35 ml) in toluene (500ml). The organic matter to remove salts by water washing operation was purified with activated carbon column chromatography (toluene). There was thus obtained 2- (4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl) pyridine (11.2 g).
References: [1] Patent: US2013/231489, 2013, A1, . Location in patent: Paragraph 0184; 0185.
[2] Patent: JP5673362, 2015, B2, . Location in patent: Paragraph 1082; 1084.
  • 3
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  • [ 73183-34-3 ]
  • [ 908350-80-1 ]
References: [1] Angewandte Chemie - International Edition, 2019, vol. 58, # 16, p. 5392 - 5395[2] Angew. Chem., 2019, vol. 131, # 16, p. 5446 - 5449,4.
 

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