Structure of 13438-50-1
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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. : | 13438-50-1 |
Formula : | C16H9Br |
M.W : | 281.15 |
SMILES Code : | BrC4=C2C=CC=C3C1=CC=CC=C1C(=C23)C=C4 |
MDL No. : | MFCD07787460 |
InChI Key : | WCXFCLXZMIFHBU-UHFFFAOYSA-N |
Pubchem ID : | 13221800 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 16 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 76.08 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.91 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.79 |
Solubility | 0.000457 mg/ml ; 0.00000163 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.33 |
Solubility | 0.00131 mg/ml ; 0.00000466 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.43 |
Solubility | 0.0000104 mg/ml ; 0.0000000371 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) |
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 |
-4.06 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) |
2.19 |
* 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 |
---|---|---|
94% | With bromine; In nitrobenzene; at 20℃; for 20h; | Preparation of Compound 2-1 [102] 50 g (247 mmol) of fluoranthene was dissolved in 1 L of nitrobenzene, and 12 mL (234.7 mmol) of bromine diluted with 200 mL of nitrobenzene was slowly added in droplets thereto. After the solution was completely added in droplets, the reaction solution was stirred at room temperature for 20 hours. The reaction solution was added with 500 mL of aqueous saturated sodium thiosulfate chloride so that the reaction was terminated. The mixture thus obtained was extracted with 3 L of EA and then washed with 1 L of distilled water. The resultant organic layer was dried with anhydrous MgSO4, treated under reduced pressure to remove the organic solvent, filtered using silica gel, and then recrystallized, thus obtaining Compound 2-1 (65 g, 94percent |
80% | With N-Bromosuccinimide; In acetonitrile; at 20℃; for 24h; | Preparation of compound 1-2 [95] After dissolving compound 1-1 (50 g, 247.2 mmol) in MeCN (50mL) and adding N-bromosuccinimide (NBS) (44 g, 247.2 mmol), the reaction mixture was stirred for 1 day at room temperature. After terminating the reaction, the reaction mixture was extracted with ethyl acetate (EA), and the organic layer was concentrated and purified through silica column to obtain compound 1-2 (55.6 g, 80 percent). |
75% | With N-Bromosuccinimide; In acetonitrile; at 20℃; for 18h; | 50 g (0.247 mol) of fluoranthene was placed in a 500 mL flask and 150 mL of MeCNDissolve. 48.4 g (0.272 mol) of NBS was slowly added at room temperature, and the mixture was stirred at room temperature for 18 hours. The reactionUpon completion, 30 mL of a small amount of MeCN is added and stirred, followed by filtration. The resulting solid was washed again with MeOH (1 L)(Yield: 75percent) of a yellow solid compound (Intermediate (10)). |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 50℃; for 2h;Inert atmosphere; | Synthesis Example 3Synthesis of 3-(4-bromophenyl)fluoranthene; Under the atmosphere of argon, 62 g of fluoranthene and 250 ml of dehydrated DMF (manufactured by HIROSHIMA WAKO Co., Ltd.) were placed into a 500 ml flask and heated at 80° C. After the material was dissolved, 60 g of N-bromosuccinimide (manufactured by HIROSHIMA WAKO Co., Ltd.) was added at 50° C., and the resultant mixture was stirred for 2 hours. After the reaction was completed, the reaction solution was poured into 500 ml of purified water, and formed crystals were separated by filtration. The separated crystals were purified in accordance with the column chromatography, and 10.5 g of crystals were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With sodium t-butanolate;palladium diacetate; tri-tert-butyl phosphine; In toluene; at 90℃; for 50h; | Example 1 A compound of the structural formula (1) was synthesized as follows. 3-Bromofluoranthene (9.0 g, 32 mmol) was first added in three portions to a mixture of toluene (200 ml), tri(t-butyl)phosphine (0.4 g, 20 mmol), palladium acetate (0.1 g, 4.5 mmol), N,N-diphenylbenzidine (4.8 g, 14 mmol), and sodium t-butoxide (4.8 g, 50 mmol), and reacted by heating at 90° C. for 50 hours. The resultant reaction mixture was cooled to room temperature, and then crystals were collected by filtration and washed with a small amount of toluene. The crude product was purified by silica gel chromatography, and the resultant product was purified by sublimation to obtain a compound (3.5 g; 34percent) of the structural formula (1). With respect to the compound obtained, peaks were measured by (a) mass spectrometric analysis (MS), (b) nuclear magnetic resonance analysis (NMR), (c) ultraviolet-visible absorption spectrum analysis (UV-VIS), and (d) fluorescence spectrum, and the following results were obtained. (a) MS [TOF] m/z=736.4 [(M+)](b) 1H-NMR (400 MHz, CDCl3); 7.00 (m, 2H), 7.10-7.18 (8H), 7.20-7.28 (4H), 7.30-7.47 (12H), 7.65 (d, 2H, J=8.5 Hz), 7.70-7.80 (8H) (c) UV-VIS absorption spectrum peak 443 nm (d) Fluorescence spectrum peak 543 nm (in dioxane) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Preparation of Compound 2-2 [104] 24.5 g (87.1 mmol) of Compound 2-1 was dissolved in 500 mL of THF, cooled to -78, added with 45 mL of n-BuLi (2.5 M in hexane), and then stirred for 1 hour. Subsequently, this mixture was added with 15 mL of B(OMe)3 and stirred for 2 hours, and the reaction was terminated with 250 mL of aqueous ammonium chloride. The mixture thus obtained was extracted with 1 L of EA and then washed with 200 mL of distilled water. The resultant organic layer was dried with anhydrous MgSO4, treated under reduced pressure to remove the organic solvent, and then recrystallized, thus obtaining Compound 2-2 (14 g, 65percent). | |
Under the atmosphere of argon, 10.0 g of the crystals obtained above, 120 ml of dehydrated ether (manufactured by HIROSHIMA WAKO Co., Ltd.) and 120 ml of dehydrated toluene (manufactured by HIROSHIMA WAKO Co., Ltd.) were placed into a 500 ml flask, and the resultant mixture was cooled at -64° C. in a dry ice bath. To the cooled mixture, 25 ml of a 1.6 M hexane solution of butyllithium (manufactured by HIROSHIMA WAKO Co., Ltd.) was added dropwise over 30 minutes, and the reaction was allowed to proceed at -64° C. for 2 hours. To the resultant reaction mixture, 8 g of triisopropyl borate (manufactured by TOKYO KASEI Co., Ltd.) was added dropwise over 20 minutes. After the addition was completed, the temperature was adjusted at the room temperature, and the reaction mixture was stirred for 12 hours. After the resultant reaction mixture was cooled with ice, 100 ml of 2 N hydrochloric acid was added at a temperature of 10° C. or lower, and 25 ml of toluene was added. The organic phase separated from the resultant mixture was dried with sodium sulfate and concentrated under a reduced pressure. Hexane was added to the resultant solution, and formed crystals were separated by filtration. The obtained crystals were dissolved into 120 ml of tetrahydrofuran. To the resultant solution, 15 ml of concentrated hydrochloric acid and 0.15 g of tetrabutylammonium bromide were added, and the resultant mixture was stirred for 12 hours. The formed crystals were separated by filtration and dried, and 7.0 g of crystals of 3-fluorantheneboric acid were obtained. |