Structure of 39229-12-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 39229-12-4 |
Formula : | C14H9BrO2 |
M.W : | 289.13 |
SMILES Code : | O=C(C1=CC=C(Br)C=C1)C(C2=CC=CC=C2)=O |
MDL No. : | MFCD00223484 |
InChI Key : | REKFALFAMJBFCR-UHFFFAOYSA-N |
Pubchem ID : | 236701 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 69.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.52 |
Solubility | 0.00871 mg/ml ; 0.0000301 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.49 |
Solubility | 0.00932 mg/ml ; 0.0000322 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.66 |
Solubility | 0.000637 mg/ml ; 0.0000022 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) |
Yes |
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 |
-5.17 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 |
1.0 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) |
1.61 |
* 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 |
---|---|---|
90% | With water; copper; Selectfluor; In acetonitrile; at 20℃; for 4h; | General procedure: 1 or 3 (0.2 mmol), Cu(0) powder (0.64 mg, 5 mo%), Selectfluor (141.7 mg, 0.4 mmol, 2equiv), and CH3CN:H2O = 50:1 (V/V, 2 mL) were added to a 10-mL flask. Then the reaction mixture was stirred at room temperature for given times (see Table 2). Upon completion, the resulting mixture was diluted with CH2Cl2 (10 mL) and filtered through Celite. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100-200 mesh) using petroleum ether-EtOAc (20/1-3/1) as eluent to give pure 2 or 4. |
83.9% | With Oxone; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [Ru(cymene)Cl2]2; sodium hydrogencarbonate; In nitromethane; water; at 20℃; for 12h; | General procedure: Alkyne (0.2 mmol), Oxone (330.0 mg), NaHCO3 (41.0 mg) were added to test tube. Nitromethane (4.0 mL) and water (0.5 mL) was added via syringe. A [Ru(cymene)Cl2]2 solution (10uL, 0.004 mM in distilled nitromethane, 0.02% equiv) and 3.12 mg TEMPO which were diluted by nitromethane were added into the tube. The reaction mixture was placed under air, stirred for 12h. And it must be noted that the mixture should be stirred vigorously. It was then quenched (consumption of residual Oxone) with saturated Na2SO3 solution and reaction mixture was extracted with ethyl acetate (3×4 mL). The organic layer was separated and dried with Na2SO4. Removal of solvent followed by flash column chromatographic purification afforded products. |
82% | With ammonium iodide; potassium ethyl xanthogenate; In water; dimethyl sulfoxide; at 130℃; for 12h;Schlenk technique; | General procedure: A mixture of 1,2-diphenylethyne (1.0 mmol) and EtOCS2K (1.2 mmol) and NH4I (2.0 mmol) in 3 mL of DMSO/H2O (2:1) were stirred for 12 hours at 130 oC. Monitoring with TLC and GC-MS analysis was used to show the starting materials were completely consumed. After the reaction was finished, the reaction mixture was cooled to room temperature, the solution was filtered though a small amount of silica gel. The residue was purified by silica gel preparative TLC (n-hexane: EtOAc = 20:1), which furnished benzyl as a pale-yellow solid |
82% | With ammonium iodide; potassium ethyl xanthogenate; In water; dimethyl sulfoxide; at 130℃; for 12h; | In the reaction tube, 128 mmg (0.51 mmol) of 1-bromo-4-(phenylethynyl)benzene was added, Potassium ethyl xanthate 96 mmg (0.60 mmol), ammonium iodide 145 mmg (1.00 mmol), dimethyl sulfoxide 2 mL, water 1 mL. The reaction was stirred at 130 C for 12 hours. At the end of the reaction, 10 mL of ethyl acetate was added to quench the reaction. After washing with 6 mL of saturated brine, the organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate (the amount of ethyl acetate was 6 mL). The organic phase was combined and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, The title product 1-(4-bromophenyl)-2-phenylethane-1,2-dione was isolated by column chromatography to give a yield of 82%. |
72% | With iodine; dimethyl sulfoxide; sodium sulfate; In ethanol; ethyl acetate; | (ii) Synthesis of 1-(4-bromophenyl)-2-phenylethanedione A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (C-2). 10.0 g (38.9 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 4.7 g (18.5 mmol) of iodine, and 100 mL of dimethyl sulfoxide were placed in a 300-mL three-neck flask, and the mixture was stirred at 155 C. for 4 hours. After the reaction, the reaction solution was cooled, then the reaction solution was put into a 1 wt % sodium sulfate aqueous solution. The precipitated solid was collected by suction filtration. The residue was dissolved into ethanol, and the insoluble part was filtered off through celite. The filtrate was concentrated, and the obtained solid was dissolved into ethyl acetate. The insoluble part was filtered off again by celite-filtration, and the filtrate was concentrated. A first recrystallization was performed on the obtained solid with ethyl acetate and hexane, giving 1.5 g of the target substrate as a solid. A second recrystallization was performed on the filtrate with acetone and hexane, giving 6.7 g of the target substrate as a solid. By the two-time recrystallization, 8.2 g of the product was obtained in the yield of 72%. |
72% | With iodine; at 155℃; for 4h; | In the synthesis a (4-bromophenyl) phenylacetylene 10.0g (38.9mmol), iodine 4.7g (18.5mmol), dimethyl sulfoxide, and put into a 100mL three-necked 300mL flask was stirred for 4 hours at 155 . After the reaction, the reaction solution was cooled, then, one of theBy putting the reaction solution in the amount of% sodium sulfate aqueous solution, to precipitate a solid. After the precipitated solid collected by suction filtration, and the recovered filtrate was dissolved in water, ethanol, passed through Celite and filtered, and the filtrate was concentrated. The solid obtained was dissolved in ethyl acetate, it was passed again by Celite filtration, and the precipitated solid was filtered concentrated. The obtained solid to obtain a target product as a result of the solid was recrystallized from ethyl acetate-hexane 1.5g. Target substance added the filtrate obtained after the solid with acetone, the desired product as a result of the solid was recrystallized again from hexane to give 6.7g.Solid target compound obtained by two recrystallization is combined 8.2g, yield was 72%. |
72% | With [bis(acetoxy)iodo]benzene; toluene-4-sulfonic acid; In tetrahydrofuran; at 25℃; for 0.0833333h; | The 0.3 mmol 1 - bromo -4 - (phenyl ethynyl) benzene, 0.6 mmol paratoluene sulfonic acid, 0.3 mmol iodobenzene diacetate is added to 15 ml thick-wall pressure in the reaction tube, add 3 ml tetrahydrofuran as the solvent. Then, for the 25 C under magnetic stirring 5 minutes. To be after the reaction is complete, the reaction liquid medicine spoon column to add two chromatography silica gel (100 - 200 mesh), and the solvent is removed by reduced pressure distillation, column chromatography separation through such as the structural formula shown in the pure product (petroleum ether/ethyl acetate=5:1 as the eluant). The material is a yellow solid, yield 72%. |
71% | With iodine; dimethyl sulfoxide; at 155℃; for 4h; | A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (B-5). In a 300 mL three-necked flask were placed 7.4 g (28 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 3.7 g (14 mmol) of iodine, and 70 mL of dimethyl sulfoxide. The solution was stirred at 155 C. for 4 hours under a stream of nitrogen. After a predetermined time, the solution was cooled to room temperature and added to about 200 mL of a 1 wt % aqueous sodium thiosulfate solution; then, a solid was precipitated. The solid was collected by suction filtration. The obtained solid was dissolved in ethyl acetate, and the solution was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The filtrate was condensed to obtain a solid. The obtained solid was recrystallized with ethyl acetate/hexane; thus, 4.5 g of target pale-yellow powder was obtained with a yield of 71%. |
71% | With iodine; dimethyl sulfoxide; at 155℃; for 4h; | A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (A-2). In a 300 mL three-necked flask were placed 7.4 g (28 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 3.7 g (14 mmol) of iodine, and 70 mL of dimethyl sulfoxide. The solution was stirred under nitrogen stream at 155 C for 4 hours. After a predetermined time, the solution was cooled to room temperature and added to a 1 wt% aqueous sodium thiosulfate solution; then, a solid was precipitated. The solid was collected by suction filtration. The obtained solid was dissolved in ethyl acetate, and the solution was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The filtrate was condensed to obtain a solid. The obtained solid was recrystallized with ethyl acetate/hexane; thus, 4.5 g of target pale-yellow powder was obtained with a yield of 71 %. |
60% | With magnesium bromide diethyl etherate; oxygen; In acetonitrile; for 24h;Irradiation; | Typical procedure: A solution of diphenylacetylene (1, 0.3 mmol) and MgBr2·OEt2 (0.3 mmol) in dry MeCN (5 mL) in a pyrex test tube, purged with an O2-balloon, is stirred and irradiated externally with four 22 W fluorescent lamps, which are equipped in the distance of 65 mm, for 24 h. The reaction mixture is washed with aq. Na2S2O3 and brine, concentrated in vacuo, and purified by PTLC. |
With iodine; dimethyl sulfoxide; sodium sulfate; In ethanol; ethyl acetate; | (ii) Synthesis of 1-(4-bromophenyl)-2-phenylethanedione A synthesis scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (B-2). Into a 300-mL three-neck flask were added 10.0 g (38.9 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong> synthesised by (i), 4.7 g (18.5 mmol) of iodine, and 100 mL of dimethyl sulfoxide, and the mixture was stirred at 155 C. for 4 hours. After the reaction, the reaction solution was cooled and then put into a 1 wt % sodium sulfate aqueous solution to precipitate a solid. The precipitated solid was collected by suction filtration. The collected residue was dissolved in ethanol, and then the solution was filtered through Celite. The filtrate was concentrated, and the obtained solid was dissolved in ethyl acetate. The solution was filtered again through Celite. The filtrate was concentrated to precipitate a solid. The obtained solid was recrystallized with ethyl acetate and hexane, giving 1.5 g of the target product as a solid. The filtrate from which the solid of the target product has been obtained was again recrystallized with acetone and hexane, giving 6.7 g of the target product as a solid. The total weight of the solid of the target product obtained by the two-time recrystallization was 8.2 g and the yield of the product was 72 %. |
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