Structure of 5408-56-0
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CAS No. : | 5408-56-0 |
Formula : | C12H7IO |
M.W : | 294.09 |
SMILES Code : | IC1=CC=C2OC3=CC=CC=C3C2=C1 |
MDL No. : | MFCD00092649 |
InChI Key : | MNKSJEJNCQWHFE-UHFFFAOYSA-N |
Pubchem ID : | 223327 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 13 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 66.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
13.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.77 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.63 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.36 |
Solubility | 0.0013 mg/ml ; 0.00000441 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.78 |
Solubility | 0.00491 mg/ml ; 0.0000167 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.9 |
Solubility | 0.000367 mg/ml ; 0.00000125 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-4.71 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 |
1.0 |
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 |
1.0 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) |
3.08 |
* 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 |
---|---|---|
77% | With sulfuric acid; iodine; periodic acid; In water; acetic acid; at 60℃; for 4.5h; | [Step 1: Method of Synthesizing 2-Iododibenzofuran]In a 500-mL three-neck flask was put a suspension of 8.4 g (50 mmol) of dibenzofuran, 6.2 g (25 mmol) of iodine, 5.7 g (25 mmol) of orthoperiodic acid, 150 mL of glacial acetic acid, 30 mL of water, and 500 muL of sulfuric acid, and the suspension was heated and stirred at 60 C. for 4.5 hours to cause a reaction.After the reaction, the reaction mixture was further stirred at room temperature for 16 hours. The generated precipitate was collected by filtration, and the resulting matter was dissolved in 150 mL of toluene. Then, the solution was washed with water three times. Magnesium sulfate was added to the toluene solution to adsorb moisture.This solution was filtered, and the resulting filtrate was concentrated. Then, hexane was added thereto, followed by irradiation with ultrasonic waves. The generated solid was collected by filtration and dried, so that the objective substance was obtained as 11.3 g of white powder in 77% yield. A reaction scheme of this synthesis method is shown in (B-1) below. The compound obtained in Step 1 was subjected to a nuclear magnetic resonance (NMR) measurement. The measurement data are shown below.1H NMR (CDCl3, 300 MHz):delta (ppm)=7.33-7.38 (m, 2H), 7.48 (dt, J=1.5 Hz, 8.4 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.72 (dd, J=2.1 Hz, 8.4 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.27 (d, J=1.5 Hz, 1H).The measurement results confirmed that the objective substance, 2-iododibenzofuran, was obtained. |
77% | With iodine; periodic acid;sulfuric acid; In water; acetic acid; at 60℃; for 4.5h; | Step 1: Method of Synthesizing 2-Iododibenzofuran In a 500 mL three-neck flask was put a suspension of 8.4 g (50 mmol) of dibenzofuran, 6.2 g (25 mmol) of iodine, 5.7 g (25 mmol) of orthoperiodic acid, 150 mL of glacial acetic acid, 30 mL of water, and 500 muL of sulfuric acid, and the suspension was heated and stirred at 60 C. for 4.5 hours to cause a reaction. After the reaction, the reaction mixture was further stirred at room temperature for 16 hours. The generated precipitate was collected by filtration, and this obtained residue was dissolved in 150 mL of toluene. Then, the solution was washed with water three times. Magnesium sulfate was added to the toluene solution to adsorb moisture. This solution was filtered, and the obtained filtrate was concentrated. Then, hexane was added thereto, and the mixture was irradiated with ultrasonic waves. The generated solid was collected by filtration and dried to give 11.3 g of a white powder in 77% yield, which was the object of the synthesis. A reaction scheme of the above synthesis method is illustrated in (B-1) below. The compound obtained in Step 1 above was subjected to nuclear magnetic resonance (NMR) spectroscopy. The measurement data are shown below. 1H NMR (CDCl3, 300 MHz): delta (ppm)=7.33-7.38 (m, 2H), 7.48 (dt, J=1.5 Hz, 8.4 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.72 (dd, J=2.1 Hz, 8.4 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.27 (d, J=1.5 Hz, 1H). |
30.4% | With [bis(acetoxy)iodo]benzene; sulfuric acid; iodine; acetic anhydride; acetic acid; for 2h; | Exemplified Compound 1-1, 30 g (0.178 mol)340 ml of acetic acid, 60 ml of acetic anhydride and 26.1 g (× 0.455 mol) of iodobenzene diacetate were mixed and dissolved by stirring. To this solution, 20.6 g (× 0.455 mol) of iodine and 0.5 ml of sulfuric acid were alternately added in 10 minutes. And the mixture was further stirred for 2 hours.Precipitated crystals were filtered under reduced pressure. 100 ml of ethanol was added to the obtained crystals, and the suspension was refluxed for 30 minutes. After stirring at room temperature for 1 hour, filtration under reduced pressure gave exemplified compound 3-1, 15.9 g. (Yield 30.4%) |
Dibenzofuran (10.0 g, 59.4 mmol) and periodic acid (16.2 g, 71.3 mmol) were dissolved in acetic acid (600 ml) and iodine (9.0 g, 71.3 mmol) was added to the solution. The solution was stirred at 60C for 30 min followed by addition of distilled water (120 ml) and sulfuric acid (1.20 ml). The solution was refluxed for 12 h, cooled to room temperature and poured into distilled water. White powder was filtered off and then the filtrate was extracted using ethyl acetate. The extracted solution was washed with 5% NaOH solution and aqueous sodium sulfate. Ethyl acetate was removed by evaporation and yellowish white powder was obtained (12.0 g, yield: 69%) after drying in vacuum. 2-Iododibenzofuran was included 85% of all powder and it was used in amination without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.3% | EXAMPLE 6 A 100 ml three-necked glass container was charged with 4.20 g (25 millimoles) of dibenzofurane, 6.35 g (25 millimoles) of iodine, 50 ml of acetic acid, 25 ml of chloroform, 2 ml of sulfuric acid and 2 ml of water, and the reaction was carried out at 90 C. for 6 hours. Nitrogen as containing NO2 was blown into the reaction mixture at a rate of 30 ml/min. The total amount of NO2 fed was 56.5 millimoles. The reaction product was extracted with chloroform, and analyzed by gas chromatography. There was no unreacted material, and 2,8-diiododibenzofurane and 2-iododibenzofurane were obtained in a yield of 94.6% and 5.4%, respectively. The iodination yield was 97.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N2;tris-(dibenzylideneacetone)dipalladium(0); Pd2(dba)3; In tetrahydrofuran; 5,5-dimethyl-1,3-cyclohexadiene; hexane; dichloromethane; toluene; | A mixture of 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (12 g, 32.5 mmol), 3-bromo-9H-carbazole (6.66 g, 27.1 mmol), and potassium phosphate (34.5 g, 162 mmol) in 500 mL of toluene and 50 mL of H2O was bubbled with N2 for 20 min. Dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (0.445 g, 1.083 mmol) and Pd2(dba)3 (0.248 g, 0.271 mmol) were then added, and the mixture was heated to reflux under N2 for 5 h. TLC indicated the reaction was done. The reaction was extracted with dichloromethane and washed with brine and dried with magnesium sulfate. The solution was heated up to boil. Hexane was added. The dichloromethane was boiled off and hexanes volume reached about 1200 mL. Precipitate formed during boiling off dichloromethane. The solution was cooled to room temperature and stirred overnight. The precipitate was filtered and dissolved in THF and ran a short silica gel plug. After dried under vacuum at 60 C., 9.6 g (87%) of product was obtained. Synthesis of Compound 1. A mixture of <strong>[5408-56-0]2-iododibenzo[b,d]furan</strong> (2.59 g, 8.81 mmol), 9-phenyl-9H,9'H-3,3'-bicarbazole (3 g. 7.34 mmol), and sodium t-butoxide (1.764 g, 18.36 mmol) in 200 mL of xylene was bubbled with N2 for 20 min. Dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (0.121 g, 0.294 mmol) and Pd2(dba)3 (0.067 g, 0.073 mmol) were then added, and the mixture was heated to reflux under N2 for 24 h. The mixture was cooled and filtered through Celite. After solvent evaporation, the residue was coated on Celite and purified by column chromatography 3.7 g of product was obtained after column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In xylene; for 24h;Inert atmosphere; Reflux; | Compound 1[0130] Synthesis of Compound 1. A mixture of <strong>[5408-56-0]2-iododibenzo[b,d]furan</strong> (2.59 g, 8.81 mmol), 9-phenyl-9H,9'H-3,3'-bicarbazole (3 g, 7.34 mmol), and sodium t-butoxide (1.764 g, 18.36 mmol) in 200 mL of xylene was bubbled with N2 for 20 min. Dicyclohexyl(2',6'- dimethoxybiphenyl-2-yl)phosphine (0.121 g, 0.294 mmol) and Pd2(dba)3 (0.067 g, 0.073 mmol) were then added, and the mixture was heated to reflux under N2 for 24 h. The mixture was cooled and filtered through Celite. After solvent evaporation, the residue was coated on Celite and purified by column chromatography 3.7 g of product was obtained after column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sulfuric acid; iodine; magnesium sulfate; In hexane; water; acetic acid; toluene; | Step 1: Synthesis of 2-Iododibenzofuran In a 500-mL three-neck flask, a suspension of 8.4 g (50 mmol) of dibenzofuran, 6.2 g (25 mmol) of iodine, 5.7 g (25 mmol) of orthoperiodic acid, 150 mL of glacial acetic acid, 30 mL of water, and 500 muL of sulfuric acid was heated and stirred at 60 C. for 4.5 hours. After that, the mixture was stirred at room temperature for 16 hours. The generated precipitate was collected by filtration, and the resulting matter was dissolved in 150 mL of toluene and a toluene solution was made. This toluene solution was washed with water three times. After the washing, magnesium sulfate was added to the toluene solution to adsorb moisture. This mixture was filtered and the given filtrate was concentrated. After that, hexane was added, and the mixture was irradiated with ultrasonic waves to perform recrystallization, so that 11.3 g of white powder, which was the objective substance, was obtained in 77% yield. A synthetic scheme of Step 1 is shown in (a-1) below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[Step 1: Method of Synthesizing Dibenzofuran-2-boronic Acid] In a 500-mL three-neck flask was put 8.8 g (30 mmol) of <strong>[5408-56-0]2-iododibenzofuran</strong>, and the atmosphere in the flask was replaced by nitrogen. Then, 200 mL of dehydrated tetrahydrofuran (abbreviation: THF) was added thereto and the mixture was cooled to -78 C. To this mixture was dripped 22 mL (36 mmol) of an n-butyllithium hexane solution (1.63 mol/L), and the mixture was stirred for 4 hours to cause a reaction. To this reaction mixture was added 4.6 mL (45 mmol) of trimethyl borate, and the mixture was stirred at -78 C. for 2 hours and at room temperature for 20 hours. After the reaction, diluted hydrochloric acid was added to this reaction solution until the mixture was made acid, and then the mixture was stirred for 2 hours. The stirred solution was subjected to extraction with ethyl acetate, and the obtained organic layer was washed with a saturated aqueous solution of sodium chloride. After the washing, magnesium sulfate was added to the organic layer to adsorb moisture. This suspension was filtered, and the resulting filtrate was concentrated to give an objective substance. A reaction scheme of this synthesis method is shown in (C-1) below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With sodium t-butanolate;tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); In hexane; xylene; at 120℃; for 5h;Inert atmosphere; | [Step 2: Method of Synthesizing N-(Dibenzofuran-2-yl)-phenylamine (Abbreviation: FrA)]In a 100-mL three-neck flask were put 4.5 g (15 mmol) of <strong>[5408-56-0]2-iododibenzofuran</strong>, 2.0 g (20 mmol) of aniline, 45 mg (0.1 mmol) of bis(dibenzylideneacetone)palladium(0), and 3.0 g (30 mmol) of sodium-tert-butoxide (abbreviation: tert-BuONa), and 30 mL of dehydrated xylene was added. Then, deaeration was performed for 3 minutes until no bubbles came out. To this suspension, 0.5 mL (0.3 mmol) of tri-tert-butylphosphine (10 wt % hexane solution) was added, and then the mixture was heated and stirred at 120 C. for 5 hours in a nitrogen atmosphere to cause a reaction.About 200 mL of toluene was added to this reaction suspension, and the mixture was filtered through Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135), alumina, and Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The resulting filtrate was washed with water, and magnesium sulfate was added thereto to adsorb moisture.This suspension was further filtered through Florisil, alumina, and Celite, and the resulting filtrate was concentrated. Then, methanol was added thereto, followed by irradiation with ultrasonic waves. The generated solid was collected by filtration and dried, so that the objective substance was obtained as 1.6 g of white powder in 39% yield. A reaction scheme of this synthesis method is shown in (B-2) below. The Rf values of the objective substance, <strong>[5408-56-0]2-iododibenzofuran</strong>, and aniline were respectively 0.28, 0.59, and 0.07, which were found by silica gel thin layer chromatography (TLC) (with a developing solvent of ethyl acetate and hexane in a ratio of 1:10).The compound obtained in Step 2 was subjected to a nuclear magnetic resonance (NMR) measurement. The measurement data are shown below.1NMR (CDCl3, 300 MHz):delta (ppm)=5.80 (s, 1H), 6.94-7.68 (m, 10H), 8.99 (d, J=7.8 Hz, 1H), 8.11 (s, 1H).The measurement results confirmed that the objective substance, N-(dibenzofuran-2-yl)-phenylamine (abbreviation: FrA), was obtained. |
39% | With sodium t-butanolate;tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); In hexane; xylene; at 120℃; for 5h;Inert atmosphere; | Step 2: Method of Synthesizing N-(Dibenzofuran-2-yl)-phenylamine (Abbreviation: FrA) Into a 100 mL three-neck flask were placed 4.5 g (15 mmol) of <strong>[5408-56-0]2-iododibenzofuran</strong>, 2.0 g (20 mmol) of aniline, 45 mg (0.1 mmol) of bis(dibenzylideneacetone)palladium(0), and 3.0 g (30 mmol) of sodium-tert-butoxide (abbreviation: tert-BuONa), and 30 mL of dehydrated xylene was added. Then, deaeration was performed for 3 minutes until a bubble ceased to appear. To this suspension, 0.5 mL (0.3 mmol) of tri-tert-butylphosphine (a 10 wt % hexane solution) was added, and the mixture was heated and stirred at 120 C. for 5 hours in a nitrogen atmosphere to cause a reaction. About 200 mL of toluene was added to this reaction suspension, and the mixture was filtered through Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135), alumina, and Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The obtained filtrate was washed with water, and magnesium sulfate was added thereto to adsorb moisture. This suspension was further filtered through Florisil, alumina, and Celite, and the obtained filtrate was concentrated. Then, methanol was added thereto, and the mixture was irradiated with ultrasonic waves. The generated solid was collected by filtration and dried to give 1.6 g of a white powder in 39% yield, which was the object of the synthesis. A reaction scheme of the above synthesis method is illustrated in (B-2) below. The Rf values of the object of the synthesis, <strong>[5408-56-0]2-iododibenzofuran</strong>, and aniline were respectively 0.28, 0.59, and 0.07, which were found by silica gel thin layer chromatography (TLC) (ethyl acetate:hexane (1:10) as the developing solvent). The compound obtained in Step 2 above was subjected to nuclear magnetic resonance (NMR) spectroscopy. The measurement data are shown below. 1H NMR (CDCl3, 300 MHz): delta (ppm)-=5.80 (s, 1H), 6.94-7.68 (m, 10H), 8.99 (d, J=7.8 Hz, 1H), 8.11 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene;Reflux; Inert atmosphere; | A solution of 9-(3-(diphenyl(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)silyl)phenyl)-9H-carbazole (3.25 g, 5.18 mmol), 2-iododibenzo[£, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium phosphate; copper(l) iodide; trans cyclohexane-1,2-diamine; In 1,4-dioxane; at 120℃; for 72h;Inert atmosphere; | General procedure: Under a nitrogen atmosphere, a mixture of 2.4 g (5.4 mmol) of Intermediate A-7, 1.4 g (5.9 mmol) of 3-bromobiphenyl, 0.2 g (1.1 mmol) of copper iodide, 3.1 g (26.8 mmol) of tripotassium phosphate, 1.1 g (5.3 mmol) of trans-1,2-cyclohexanediamine, and 30 ml of 1,4-dioxane was prepared and heated at 120C with stirring for 72 hours. The reaction solution was cooled to room temperature, the precipitated crystal was collected by filtration, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography and Compound 1-21 weighing 1.2 g (2.0 mmol, 37% yield) was obtained as a white solid. APCI-TOFMS: m/z 600 [M+H]+. The result of 1H-NMR measurement (solvent: THF-d8) is shown in Fig. 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.9 g | <strong>[5408-56-0]2-Iododibenzofuran</strong> (11.0 g, 37.4 mmol) and carbazole (7.2 g, 43.0 mmol) were dissolved in 1,4-dioxane (250 ml) at room temperature under nitrogen. After 30 min, trans-1,2-diaminocyclohexane (2.0ml, 18.7mmol) was added to the solution and the solution was refluxed overnight. After cooling to room temperature, the solution was extracted using methylene chloride. Methylene chloride was removed by evaporation and obtained product was purified by column chromatography on silica gel using toluene/n-hexane (1: 2) as an eluent. A white powder was obtained as a product (7.9g, yield: 63%). (0007) 1H NMR (400MHZ, CDCl3): delta 8.17 (d, 2H, J=3.8Hz), 8.11 (d, 1H, J=1Hz), 7.94 (d, 1H, J=4Hz), 7.78 (d, 1H, J=4Hz), 7.66-7.59 (m, 2H), 7.54-7.50 (m, 1H), 7.41-7.35 (m, 5H), 7.31-7.25 (m, 2H). |