Structure of 3164-13-4
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
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 |
26.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.26 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.91 |
Solubility | 0.00334 mg/ml ; 0.0000122 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.62 |
Solubility | 0.00654 mg/ml ; 0.0000239 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.28 |
Solubility | 0.000143 mg/ml ; 0.000000522 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.88 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.55 |
* 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.
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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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