Structure of 667940-23-0
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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. : | 667940-23-0 |
| Formula : | C16H11Br |
| M.W : | 283.16 |
| SMILES Code : | BrC1=CC(C2=CC=C3C=CC=CC3=C2)=CC=C1 |
| MDL No. : | MFCD16658911 |
| InChI Key : | FWPXWVYUNHYGPE-UHFFFAOYSA-N |
| Pubchem ID : | 23080773 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302 |
| Precautionary Statements: | P280-P305+P351+P338 |
| Num. heavy atoms | 17 |
| Num. arom. heavy atoms | 16 |
| Fraction Csp3 | 0.0 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 0.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 77.08 |
| TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.03 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
6.1 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.27 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.35 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.26 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.0 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-6.07 |
| Solubility | 0.000242 mg/ml ; 0.000000853 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-5.88 |
| Solubility | 0.000372 mg/ml ; 0.00000131 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.44 |
| Solubility | 0.0000103 mg/ml ; 0.0000000365 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
| 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 |
-3.7 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
| 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 |
2.0 |
| 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) |
1.97 |
* 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 |
|---|---|---|
| 85% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 24h;Heating / reflux; | 2- A. Production of compound 2a; [79] After l-bromo-3-iodobenzene (10 g, 35.35 mmol) and 2-naphthalene bromic acid(5.47 g, 31.82 mmol) were dissolved in anhydrous THF (100 mL), Pd(PPh ) (1.2 g, 1.06 mmol) and 50 mL of 2M K CO aqueous solution were added and then refluxed <n="17"/>for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2a (8.5 g, 85%).[80] MS [M + H] = 283 |
| 76% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 24h;Inert atmosphere; Reflux; | Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthaleneboronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine)palladium(0), 6.4 L of toluene and 3.2 L of aqueous solution of 2M sodium carbonate were added together, and stirred while being refluxed for 24 hours. After the reaction was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was washed by water and dried with magnesium sulfate, the toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2-(3-bromophenyl)naphthalene was obtained at an yield of 76%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 24h;Heating / reflux; | 2-B . Production of compound 2; [82] After the compound 2a (4.0 g, 14.13 mmol) and the compound Id (9.43 g, 16.95 mmol) were dissolved in anhydrous THF (200 mL), Pd(PPh ) (0.49 g, 0.42 mmol) and 60 mL of 2M K CO aqueous solution were added and then refluxed for 24 hours. The organic layer was extracted by using ethyl acetate and water was removed with magnesium sulfate. The organic layer was filtered at reduced pressure and concentrated, and the solvent was removed. The resulting substance was purified by using column chromatography and then recrystallized in THF and ethanol to obtain a white solid compound 2 (6.0 g, 67%) represented by Formula 1-2. MS data in respects to the compound 2 are shown in Fig. 3.[83] MS [M + H] = 632 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | (1) Synthesis of Compound 2-1 Under an argon gas atmosphere, 243 g (1.41 mol) of 2-naphthalene boronic acid, 400 g (1.41 mol) of 3-bromoiodobenzene, 3.27 g (28.2 mmol) of tetrakis(triphenylphosphine) palladium(0), 6.4 L of toluene and 3.2 L of 2M sodium carbonate solution were mixed together, and stirred for 24 hours while being refluxed. After the reaction in the mixture was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was cleansed by water and dried with magnesium sulfate, toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 303 g of 2(3-bromophenyl)naphthalene was obtained with an yield of 76%. | |
| 75% | Synthesis Example 6 (Synthesis of 2-(3-bromophenyl)naphthalene) The same procedures as those conducted in Synthesis Example 2 were conducted except that 3-iodobromobenzene was used in place of 4-iodobromobenzene, and 20.1 g of a colorless oily substance was obtained. Since m/z=284 and 282 in FD-MS of the obtained compound, which corresponded to C16H11Br=283, the compound was identified to be 2-(3-bromophenyl)naphthalene (the yield: 75%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 47% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 24h;Heating / reflux; | Example 13 : Preparation of compound 30; [196][197] 13-A. Preparation of compound 13a[198] Under N atmosphere, 1,3-dibromophenyl (10 g, 42.2 mmol), 2-naphthyl boronic acid (5.16 g, 42.2 mmol), and Pd(PPh ) (2.4 g, 2.1 mmol) were added to a 2 M aqueous solution of potassium carbonate (50 mL) and THF (300 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, dried over magnesium sulfate, and distilled under reduced pressure. The resultant was purified by column chromatography to prepare a compound 13a (4.6 g, 47%). MS [M] = 233 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of <strong>[667940-23-0]2(3-bromophenyl)naphthalene</strong> and 3 L of dehydrated TI-IF was cooled down to minus 10 degree C., and 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium was dropped into the mixture while the mixture was being stirred. Then, the mixture was stirred at 0 degree C. for 2 hours. The reaction solution was again cooled down to minus 78 degrees C., and 450 g (2.39 mol) of triisopropylborate was dropped into the solution. Then, the solution was stirred at room temperature for 17 hours. The reaction mixture was added with aqueous solution of hydrochloric acid and stirred at room temperature for 1 hour. The reaction mixture was added with 3 L of toluene, and aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl)phenylboronic acid was obtained at an yield of 67%. | |
| 50% | 13-B. Preparation of compound 13b; [200] Under N atmosphere, to a compound 13a (4 g, 14.1 mmol) prepared in 13-A, dehydrated ether (80 mL) and dehydrated toluene (80 mL) were added, and cooled to - 640C in ice bath. A 2.5 M butyl lithium/hexane solution (6 mL) was added drop wise thereto for 30 minutes, and subjected to reaction at -640C for 2 hours. Boronic acid triisoester (9 mL) was added dropwise thereto for 15 minutes, and then stirred at room <n="75"/>temperature for 12 hours. After ice cooling, 2 N hydrochloric acid (35 rnL) was added at 1O0C or lower and toluene (10 mL) was added. The mixture was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was re- crystallized from EtOH to prepare a compound 13b (1.75 g, 50%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; toluene; | (2) Synthesis of Compound 2-2 Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of 2(3-bromophenyl) naphthalene and 3 L of dehydrated THF was cooled down to -10 degrees C., and added with 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium in drops while being stirred. Then, the reaction mixture was stirred for two hours at 0 degree C. The reaction solution was further cooled down to -78 degrees C., and added with 450 g (2.39 mol) of triisopropyl borate in drops. Subsequently, the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was further added with solution of hydrochloric acid to be stirred for one hour at room temperature. The reaction mixture was further added with 3 L of toluene, so that aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl) phenylboronic acid was obtained at an yield of 67%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 0 - 20℃; for 4h;Inert atmosphere; | Under an argon gas atmosphere, a mixture of 25.0 g (88.3 mmol) of <strong>[667940-23-0]2-(3-bromophenyl)naphthalene</strong>, 2.17 g (1.77 mmol) of PdCl2(PPh3)2, 0.67 g (3.53 mmol) of CuI and 120 mL of triethylamine was cooled down to 0 degree C., and added with 10.41 g (106 mmol) of trimethylsilylacetylene. Then, the mixture was stirred at room temperature for 4 hours. After the reaction was over, insoluble matters were removed by filtration, and the solvent was distilled away. The obtained residue was added with aqueous solution of hydrochloric acid, and extracted with toluene. After liquid separation, organic phase thereof was washed with aqueous solution of sodium hydrogencarbonate, and subsequently washed with water and saturated sodium chloride solution. The organic phase was dried with anhydrous sodium sulfate. After filtration, the solvent was distilled away. Then, the residue was refined by column chromatography, so that 19.0 g of trimethyl((3-naphthalene-2-yl)phenyl)ethynyl)silane was obtained at an yield of 72%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | With potassium phosphate; copper; In N,N-dimethyl-formamide;Reflux; | 9-bromo-11H-Benzo [a] carbazole 20g (67.53mmol), 2 - (3-bromophenyl)-naphthalene 19.1g (67.53mmol), K3PO421.50g (101.30mmol), Cu powder 6.4g (101.30mmol), the dimethylformamide was stirred under reflux using a mid-100ml. after cooling to room temperature, was filtered to remove the catalyst and the K3PO4. To give the compound 46-a 27.9g (59.43mmol, 88% yield) using a reduced pressure was purified by column chromatography and dried |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 52% | With nickel chloride hydrate; at -10℃; for 0.5h; | General procedure: To a mixture of aryl halide (0.3 mmol), NiCl2(H2O)1.5 [1] (0.0075 mmol, 2.5 mol %), was charged dry THF (1 mL). The mixture was pumped and refilled with nitrogen for three times. The resulting mixture was stirred at -10 under nitrogen for 30 min. The reaction mixture was quenched through the addition of ice MeOH, then poured into a separatory funnel containing saturated aqueous NH4Cl (ca. 5 mL) and extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine and dried over Na2SO4. The crude product was purified by column chromatography. Extent of isomerization can be easily determined via 1H NMR spectroscopy by comparison of the intergral of the singlet from the t-butyl group (1.3-1.4 ppm, 9H) to the integral of the doublet from the benzylic S3 protons of the i-butyl group (2.4-2.5 ppm, 2H). The doublet from the methyls of the i-butyl group could additionally be used (ca. 0.8 ppm, 6H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 53% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; toluene;Reflux; | General procedure: In a round-bottom flask, 37.3 g (132 mmol) of 1-bromo-4-iodobenzene, 14.2 g (125 mmol) of (1H-1,2,4-triazol-1-yl) boronic acid,Potassium carbonate 36.6g (264mmol), Pd (PPh3) 4 3g (2mmol), water 70ml, toluene 180ml and tetrahydrofuran 180ml was added and refluxed.After the reaction, the layer was separated to remove the aqueous layer and the organic layer was concentrated under reduced pressure.Column chromatography was used to obtain 22 g of 1- (4-bromophenyl) -1H-1,2,4-triazole (75% yield). |