Structure of 1714-29-0
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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. : | 1714-29-0 |
Formula : | C16H9Br |
M.W : | 281.15 |
SMILES Code : | BrC1=CC=C2C=CC3=CC=CC4=C3C2=C1C=C4 |
MDL No. : | MFCD00015767 |
InChI Key : | HYGLETVERPVXOS-UHFFFAOYSA-N |
Pubchem ID : | 159627 |
GHS Pictogram: |
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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 | 77.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.28 |
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 |
4.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.86 |
Solubility | 0.00039 mg/ml ; 0.00000139 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.45 |
Solubility | 0.00101 mg/ml ; 0.00000359 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 |
-3.98 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 |
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) |
1.53 |
* 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 sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux; | (Synthesis of Compound (AN-2)) (1) Synthesis of Intermediate [1-bromo-6-(4-naphthalene-1-yl-phenyl) pyrene] 7.4 g of 4-(naphthalene-1-yl) phenyl boronic acid prepared by a well known method and 7.0 g of conventional 1-bromopyrene were dissolved in 80 ml of dimethoxyethane (DME). Subsequently, 0.58 g of tetrakistriphenylphosphine palladium and 40 ml of 2M-sodium carbonate aqueous solution were added therein, followed by argon displacement. After heating and refluxing over 8 hours, it was stood to cool and then an organic layer was extracted therefrom by toluene. The organic layer was washed by saturated salt water, followed by drying through anhydrous sodium sulfate, and then the organic solvent was removed by an evaporator. The residue was refined through a silica gel chromatography (a developing solvent: toluene) and then 10.0 g of 1-(4-naphthalene-1-yl-phenyl) pyrene was obtained. (yield: 99 %) 10.0 g of 1-(4-naphthalene-1-yl-phenyl)pyrene obtained was dispersed into 100 ml of dimethyl formaldehyde (DMF), and 5.3 g N-bromosuccinamide (NBS) in DMF solution was dropped therein at room temperature. After stirred over 5 hours, it was left around overnight. After the overnight, 150 ml of water was added to it and the deposited crystal was filtrated, followed by water and ethanol washing of the crystal. The crystal obtained was refined through a silica gel chromatography (a developing solvent: hexane / toluene = 2 / 1) and then 4.5 g of 1-bromo-6-(4-naphthalene-1-yl-phenyl)pyrene (the yield: 38%) and 3.8 g of 1-bromo-8-(4-naphthalene-1-yl-phenyl)pyrene were obtained (the yield: 32%) as the intermediates. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 g | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 23℃;Inert atmosphere; | To a mixture of 21-bromopyrene (21.2 g, 75.3 mmole), 3-tert- butylaniline (12.3 g, 82.4 mmole) in toluene (280 ml) was added Pd2(dba)3 (1.1 g, 1.2 mmole) and tri-tert-butyl-phosphine (0.49 g, 2.4 mmole) followed by addition of sodium tert-butoxide (8.7 g, 90.5 mmole). Resulting mixture was stirred at ambient temperature under nitrogen atmosphere overnight. After that the mixture was stirred with water (20 ml), organic phase passed through a filter filled with basic alumina, Florisil®, silica gel and Celite® eluting with toluene. Toluene evaporated, the reside dissolved in hexanes and precipitate collected after 1 day to give 24 g of the product that was used for the next step without further purification.1H-NMR (toluene-d8, 500 MHz): 1.29 (s, 9H), 5.69 (s, 1H), 6.77 (dd, 1H, J1 = 2 Hz, J2 = 8 Hz), 6.96 (d, 1H, J = 8 Hz), 7.07 (t, 1H, J = 1.5 Hz), 7.15 (t, 1H, J = 8 Hz), 7.73-7.83 (m, 6H), 7.90 (d, 2H, J = 8 Hz), 7.92 (d, 1H, J = 9 Hz), . MS: MH+ = 350. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.3 g | With (3-phenylallyl)(chloro)-[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II); tetrabutylammomium bromide; potassium carbonate; In water; for 2h;Reflux; Inert atmosphere; | In a nitrogen atmosphere, <strong>[890042-13-4]4,4,5,5-tetramethyl-2-(triphenylen-2-yl)-1,3,2-dioxaborolane</strong> (3.0 g), 1-bromopyrene (2.2 g), chlorophenylallyl [1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene] palladium(II) (25 mg) as a palladium catalyst, potassium carbonate (2.2 g), tetrabutylammonium bromide (TBAB, 0.8 g), cyclopentyl methyl ether (CPME, 20 mL), and water (2 mL) were put in a flask and heated and stirred at a reflux temperature for two hours. After the reaction, the reaction solution was cooled. Water was added thereto, and the resulting mixture was stirred. Thereafter, the precipitate was filtered. The precipitate was dried, then heated and dissolved in chlorobenzene, and then filtered through a silica gel short pass column (eluent: toluene). The eluate was concentrated to obtain a solid. The solid was filtered and dried, and then subjected to sublimation purification to obtain compound (2-350) (3.3 g). The structure of compound ( 2-350) thus obtained was identified by NMR measurement. 1H-NMR (CDCl3): 7.6 to 7.7 (m, 4H), 7.9 (dd, 1H), 8.0 (m, 2H), 8.1 to 8.2 (m, 4H), 8.2 (m, 1H), 8.3 (m, 2H), 8.7 to 8.8 (m, 4H), 8.8 (d, 1H), 8.9 (d, 1H) |