Structure of 760212-58-6
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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. : | 760212-58-6 |
Formula : | C19H13BrN2 |
M.W : | 349.22 |
SMILES Code : | BrC1=CC=C(N2C(C3=CC=CC=C3)=NC4=CC=CC=C24)C=C1 |
MDL No. : | MFCD09746342 |
InChI Key : | PPYIZNYOMNYZCG-UHFFFAOYSA-N |
Pubchem ID : | 23094071 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 21 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 94.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.01 |
Solubility | 0.000339 mg/ml ; 0.00000097 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.58 |
Solubility | 0.000917 mg/ml ; 0.00000262 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.93 |
Solubility | 0.00000408 mg/ml ; 0.0000000117 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.56 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 |
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 |
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) |
2.29 |
* 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 |
---|---|---|
46% | In an argon atmosphere, 10 g (29 mmol) of 1-(4-bromophenyl)-phenyl-1H-benzimidazole were dissolved into 100 mL of dehydrated THF, and the temperature of the solution was cooled to -78 C. Then, 20 mL of n-butyllithium (in hexane, 1.6 mol/L) were dropped. After the mixture had been stirred at -78 C for 1 hour, the temperature of the mixture was increased to 0C. The temperature of the mixture was cooled to -78 C again, and 9.7 mL (87 mmol) of trimethoxyborane were dropped. The mixture was stirred at -78 C for 1 hour, and was then stirred at room temperature for 2 hours. 100 mL of 10-mass% hydrochloric acid were added, and the whole was stirred for 1 hour, followed by filtration. The organic layer of the filtrate was washed with a saturated sodium chloride solution and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by means of silica gel column chromatography to obtain 4.2 g of 4-(2-phenyl-1H-benzimidazol-1-yl)phenylboronic acid (46% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux; | 1.0 g (2.9 mmol) of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole, 1.5 g (3.2 mmol) of 9,10-di(2-naphtyl)anthracene-2-boronic acid, and 0.067 g (0.058 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 1.7g of a greenish white solid (84% yield) . Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 698 with respect to a molecular weight of 698.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.41% | In a 1000 ml three-necked flask, equipped with mechanical stirring, Ar gas protection, add 25. lg of the bromine synthesized in the third step (molecular weight 348, 0.072 mol 1), 300 ml of anhydrous THF, cooled to -78 C, stirred 35ml of BuLi (2 · 4M, 0.084mol) was added dropwise, the temperature was maintained at _78 C, and after stirring for 10 min, 40 ml of B(0iPr) 3 (molecular weight 188.07, specific gravity 0.9574, 0.204 mol) was added dropwise at -78 C. After stirring to room temperature (with 3 hrs), dilute acid is added to hydrolyze, the aqueous layer is separated, neutralized to neutrality, sodium chloride is added, hydrazine HF dissolved in water is distilled off under reduced pressure, and a white solid is precipitated and filtered to obtain a product. 21 g of solid product, yield 93.41%. | |
80% | Under nitrogen protection,In a 1000ml three-neck bottle,30 g (85.96 mmol, 1 eq) of the compound 1- (4-bromophenyl) -2-phenyl-1H-benzo [d] imidazole was added to 300 mL of tetrahydrofuran,Cooling down to minus 78 degrees,39.4 mL (94.56 mmol, 1.1 eq) of n-BuLi was slowly added dropwise to the above reaction solution,Incubation reaction for 1.5h,Subsequently, 32.3 g (171.92 mmol, 2 eq) of triisopropyl borate was slowly added dropwise to the above reaction solution,Naturally warmed to room temperature and stirred overnight to stop the reaction,Add 100 mL of a 1 mol / L dilute hydrochloric acid solution and stir at room temperature for 1 h.The layers were separated, and the aqueous phase was extracted with 200 mL of dichloromethane * 1. The organic phases were combined.Spin-drying gave 21.67 g of a white solid with a yield of 80%. | |
76.8% | With n-butyllithium; In tetrahydrofuran; at -78℃; | Synthesis of Intermediate 5-D: In a 250ml three-necked round flask, added was Intermediate 5-C(11.5g, 0.03mol), and 120ml dried THF that underwent treatment with Na /Benzophenone. Liquid nitrogen was used to cool reaction to -78C. While stirring, slowly added dropwise 14.5ml of n-butyllithium (0.036mol, 2.5mol·L-1), and Triisopropyl borate 9.96ml (8.12g, 0.043mol). After the addition was completed, stirred to room temperature. Adding an appropriate amount of dilute hydrochloric acid, hydrolysis, extraction with ethyl acetate, the combined organic phases. The organic solvent was removed by rotary evaporation to give the crude product. After recrystallization from ethanol to give a white solid 7.23g, yield 76.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | 7 g of 1-(4-bromophenyl)-2-phenylbenzimidazole (0.02 mol) was added to 150 ml of THF, and the temperature was lowered to -78 C, and 12 ml (2.5 M/L, 0.03 mol) was added dropwise at -78 C. n-BuLi, keep warm for 30 minutes, add 4.26g (0.041mol) of trimethyl borate, after 2 hours of reaction, the reaction is completed, add 50ml of water to the reaction solution, stir for 20 minutes, add hydrochloric acid to adjust the pH to acidity, stir 30 The reaction solution was extracted three times with ethyl acetate. The organic layer was combined and washed with water, and then the organic phase was separated and evaporated to dryness. The solid was digested twice with petroleum ether and filtered to give 2 g of white solid intermediate A, yield 60%. |
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