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Structure of 3164-13-4

Chemical Structure| 3164-13-4

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Product Details of [ 3164-13-4 ]

CAS No. :3164-13-4
Formula : C13H8BrNO
M.W : 274.11
SMILES Code : BrC1=CC=C(C2=NC3=CC=CC=C3O2)C=C1
MDL No. :MFCD00168898
InChI Key :RBVHJNZMSBQFDK-UHFFFAOYSA-N
Pubchem ID :12846715

Safety of [ 3164-13-4 ]

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

Computational Chemistry of [ 3164-13-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 15
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 67.15
TPSA ?

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

26.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.01
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

4.36
Log Po/w (WLOGP)?

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

4.26
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.

3.47
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

4.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.84

Water Solubility

Log S (ESOL):?

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

-4.91
Solubility 0.00334 mg/ml ; 0.0000122 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.

-4.62
Solubility 0.00654 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
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

-6.28
Solubility 0.000143 mg/ml ; 0.000000522 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

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.

-4.88 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

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<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)

2.55

Application In Synthesis of [ 3164-13-4 ]

* 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 [ 3164-13-4 ]

[ 3164-13-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 3164-13-4 ]
  • [ 73183-34-3 ]
  • [ 439090-73-0 ]
YieldReaction ConditionsOperation in experiment
99% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In toluene; for 4.0h;Reflux; Inert atmosphere; 2-(4-Bromophenyl)benzo[d]azole (10 parts), bis(pinacol)diboron (10.8 parts), potassium acetate (6.9 parts) and [1,1'-double ( Diphenylphosphino)ferrocene]palladium(II) chloride dichloride adduct (1.0 part) was mixed in toluene (500 parts), and stirred at reflux temperature for 4 hours under a nitrogen atmosphere.After the obtained reaction liquid was cooled to room temperature, 20 parts of tannin was added, and the mixture was stirred for 5 minutes.Then, by separating the solid fraction by filtration, and removing the solvent under reduced pressure,2-(Benzo[d]oxazol-2-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane pentane (11.4 parts, yield 99%).
90% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100.0℃; for 8.0h; After introducing 2-(4-bromophenyl)-benzoxazole (5 g, 18.2 mmol), bis(pinacolato)diboron (5.1 g, 20.1 mmol) and potassium acetate (5.4 g, 54.7 mmol) in 1,4-dioxane (182 ml, 0.1 M) and suspension stirring the result, Pd(dppf) Cl2 (260 mg, 0.36 mmol) was added thereto, and the result was heated and stirred for 8 hours at 1000 C. After the reaction solution was cooled to room temperature, H20 (100 ml) was added thereto, the result was stirred for 10 minutes and then extracted using THF. The water layer was removed, and the organic layer was treated with magnesium sulfate (Mg504) and then concentrated. The result was crystallized with ethanol (150 ml) and then filtered to obtain a compound of Chemical Formula A (5.3 g, yield 90%). MS: [M+H]=322
81% With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 85.0℃; for 48.0h;Inert atmosphere; [0106] 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)phenyl)benzo[d]oxazole (Compound 28): A mixture of 10 (4.45 g, 16 mmol), bis(pinacolate)diborane (4.09 g, 16.1 mmol), anhydrous potassium acetate (3.14 g, 32 mmol) and Pd(dppf)Cl2 (0.48 g, 0.66 mmol) in anhydrous 1,4-dioxane (80 mL) was degassed and the resulting mixture was heated at about 85 C for about 48 hours under argon. After cooling to room temperature, the mixture was poured into ethyl acetate (-200 mL) and filtered. The filtrate was absorbed on silica gel and purified by column chromatography (hexanes/ethyl acetate, 4:1) to give a white solid (Compound 28) (4.15 g, in 81% yield).
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100.0℃; Intermediate 10 2-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-benzoxazole <n="29"/>Intermediate 9 (0.8 g), potassium acetate (0.86 g), bis(pinacolato)diboron (1.1 g) and PdCI2(dppf) (160 mg) were dissolved in anhydrous dioxane (16 ml_) and were heated at 1000C overnight. The reaction mixture was evaporated to dryness and the residue partitioned between water and DCM. The aqueous phase was separated and extracted twice with DCM. The combined organic phases were dried using a hydrophobic frit and evaporated to dryness. This was purified by ISCO Companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane to give the title compound. MS calcd for (C19H20BNO3 + H)+ : 322 MS found (electrospray) : (M+H)+ = 322
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; for 48.0h;Inert atmosphere; [0084] 2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)benzo[d]oxazole (11): A mixture of 10 (4.45 g, 16 mmol), bis(pinacolate)diborane (4.09 g, 16.1 mmol), anhydrous potassium acetate (3.14 g, 32 mmol) and Pd(dppf)Cl2 (0.48 g, 0.66 mmol) in anhydrous 1,4-dioxane (80 mL) was degassed and heated at about 85 C for about 48 hours under argon. After cooling to room temperature, the mixture was poured into ethyl acetate (-200 mL) and filtered. The filtrate was absorbed on silica gel and purified by column chromatography (hexanes/ethyl acetate, 4: 1) to give a white solid (4.15 g, in 81% yield).

  • 2
  • [ 3164-13-4 ]
  • [ 73183-34-3 ]
  • [ 357437-74-2 ]
  • [ 439090-73-0 ]
YieldReaction ConditionsOperation in experiment
With KF; potassium acetate;Pd(dppf)Cl2; In 1,4-dioxane; dichloromethane; chloroform; ethyl acetate; N,N-dimethyl-formamide; 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[d]oxazole (11): A mixture of 10 (4.45 g, 16 mmol), bis(pinacolate)diborane (4.09 g, 16.1 mmol), anhydrous potassium acetate (3.14 g, 32 mmol) and Pd(dppf)Cl2 (0.48 g, 0.66 mmol) in anhydrous 1,4-dioxane (80 mL) was degassed and heated at about 85 C. for about 48 hours under argon. After cooling to room temperature, the mixture was poured into ethyl acetate (~200 mL) and filtered. The filtrate was absorbed on silica gel and purified by column chromatography (hexanes/ethyl acetate, 4:1) to give a white solid (4.15 g, in 81% yield). Host-4 (12): A mixture of 3,6-dibromo-9-p-tolyl-9H-carbazole (2.62 g, 6.35 mmol), 10 (4.08 g, 12.7 mmol), Pd(dppf)Cl2 and KF (2.21 g, 38 mmol) in DMF (100 mL) was heated at about 120 C. under argon overnight. After the mixture was cooled to room temperature, it was poured into water (~200 mL) and filtered. The solid was collected and redissolved in chloroform (~200 mL). After the water was removed the chloroform solution was dried over Na2SO4. The chloroform solution was absorbed on silica gel, purified by column chromatography (with gradient of dichloromethane to dichloromethane/ethyl acetate 20:1), and recrystallized in dichloromethane to give a pale yellow crystalline solid (1.5 g, in 37% yield).
  • 3
  • [ 56525-79-2 ]
  • [ 3164-13-4 ]
  • [ 1215232-02-2 ]
YieldReaction ConditionsOperation in experiment
83% With tri-tert-butyl phosphine; sodium t-butanolate;bis(dibenzylideneacetone)-palladium(0); In hexane; toluene; at 80℃; for 5h;Inert atmosphere; Example 5In Example 5, a method for synthesizing 9-[4-(benzoxazol-2-yl)phenyl]-<strong>[56525-79-2]3,6-diphenyl-9H-carbazole</strong> (abbreviation: CzBOxIII) represented by Structural Formula (170), which is one of the benzoxazole derivatives of the present invention, will be specifically described. Synthesis of 9-(4-[Benzoxazol-2-yl)phenyl]-<strong>[56525-79-2]3,6-diphenyl-9H-carbazole</strong>A synthesis scheme of 9-(4-[benzoxazol-2-yl)phenyl]-<strong>[56525-79-2]3,6-diphenyl-9H-carbazole</strong> is illustrated in (G-1). In a 100 mL three-neck flask were put 1.0 g (3.7 mmol) of 2-(4-bromophenyl)benzoxazole, 1.2 g (3.7 mmol) of 3,6-diphenyl-9H-carabazole, and 0.77 g (8.0 mmol) of sodium tert-butoxide. The atmosphere in the flask was replaced with nitrogen. To this mixture were added 15 mL of toluene and 0.10 mL of a 10percent hexane solution of tri(tert-butyl)phosphine. This mixture was degassed by reducing the pressure in the flask by using an aspirator. After that, the atmosphere in the flask was replaced with nitrogen. To this mixture was added 0.030 g (0.052 mmol) of bis (dibenzylideneacetone)palladium(0), followed by stirring under a nitrogen stream at 80° C. for 5 hours. After that, toluene was added to this mixture, and this suspension was suction filtered through Celite 545 (produced by Kishida Chemical Co., Ltd., Catalog No. 020-14815), whereby a filtrate was obtained.The filtrate obtained was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine in that order. After that, magnesium sulfate was added to the organic layer to dry it. Next, this mixture was suction filtered. The resulting filtrate was concentrated to give a compound, which was then purified by silica gel column chromatography. The column chromatography was performed by using toluene as a developing solvent. The fraction obtained was concentrated to give a solid. This solid was recrystallized with a mixed solvent of dichloromethane and ethanol to give 1.8 g of a white powdered solid in a yield of 95percent.Sublimation purification of 1.8 g of the white solid obtained was performed by a train sublimation method. Under a reduced pressure of 4.0 Pa and with an argon flow rate of 5 mL/min, the sublimation purification was performed at 280° C. for 21 hours, whereby 1.5 g of the resulting substance was obtained in a yield of 83percent.The compound obtained through the above synthesis method was measured by a nuclear magnetic resonance (NMR) method. The following are the measurement data: 1H NMR (CDCl3, 300 MHz): delta=7.32-7.86 (m, 20H), 8.41 (sd, J=2.0 Hz, 2H), 8.53 (d, J=8.8 Hz, 2H)
 

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