Structure of 52057-98-4
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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. : | 52057-98-4 |
Formula : | C12H12N2O |
M.W : | 200.24 |
SMILES Code : | NC1=CC=C(C2=CC=C(OC)C=C2)N=C1 |
MDL No. : | MFCD05864840 |
InChI Key : | DUYYTOFLIZLBKH-UHFFFAOYSA-N |
Pubchem ID : | 2763993 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 60.57 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.91 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.14 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.89 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.423 mg/ml ; 0.00211 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.43 |
Solubility | 0.744 mg/ml ; 0.00372 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.32 |
Solubility | 0.00969 mg/ml ; 0.0000484 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) |
No |
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 |
-6.24 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 |
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) |
1.73 |
* 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 |
---|---|---|
With iron; ammonium chloride; In ethanol; water; at 70 - 80℃; for 1.0h; | General procedure: Ethanol (20 ml) and water (5 ml) was mixed, added with iron powder, and heated to 70-80C. Ammonium chloride (0.1 g, 2.1 mmol) was added, followed by 2-phenyl-5-nitropyridine (2.0 g, 10.0 mmol) obtained in (i). The reaction was carried out at 70-80C for 1 hour. After the completion of the reaction, the iron powder was filtered while hot through Celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in isopropyl alcohol, crystallized and filtered with addition of water to give the title compound (1.4 g, 81.9%). | |
With iron; ammonium chloride; In ethanol; water; at 70 - 80℃; for 1.0h; | General procedure: Ethanol (20 ml) and water (5 ml) was mixed, added with iron powder, and heated to 70-80C. Ammonium chloride (0.1 g, 2.1 mmol) was added, followed by 2-phenyl-5-nitropyridine (2.0 g, 10.0 mmol) obtained in (i). The reaction was carried out at 70-80C for 1 hour. After the completion of the reaction, the iron powder was filtered while hot through Celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in isopropyl alcohol, crystallized and filtered with addition of water to give the title compound (1.4 g, 81.9%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux; | General procedure: To 0.329 g (1.5 mmol) 4-iodoaniline, 1.8 mmol ArB(OH)2, 0.318 g (3 mmol) Na2CO3 and 75 mg (0.075 mmol) PdCl2(PPh3)2, 15 mL of a blended solution of dioxane and water (v/v = 3/1) was added under N2 atmosphere. Then the reaction was heated to reflux and monitored by TLC. Upon cooling, the reaction mixture was dilute with sat. NH4Cl solution, then extracted with EA (3×20 mL), and the organic layer was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography to afford different 4-aminobiphenyl derivatives. According to the reductive amination procedure, the 4-aminobiphenyl derivative was further treated with salicylaldehyde and to afford the corresponding compound 5&6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Under an atmosphere of N2, 0.175 g (1 mmol) compd. 2 was dissolved in methanol, 0.11 mL (1.05 mmol) salicylaldehyde was added and stirred overnight at room temperature. When compd. 2 disappeared, NaBH4 (61 mg, 1.6 mmol) was added. After stirring for 10 min, the reaction was quenched by sat. NH4Cl solution, then extracted with CH2Cl2 (3×20 mL), and the organic layer was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE:EtOAc = 15:1) to afford 0.230 g (82%) E6 as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With N-ethyl-N,N-diisopropylamine; In propan-1-ol; at 100℃;Sealed tube; | To a suspension of 9-substituted-2,6-dichloro-9H-purine (8)(2.00 mmol) in a mixture of n-propanol (10 mL) and N,N-diisopropyl-N-ethylamine (6.00 mmol), appropriate amine (2.05 mmol)was added. The suspension was heated while stirring in a sealedtube under an argon atmosphere at 100 C for 2-6 h. The reactionwas checked by TLC using mobile phase toluene-ethylacetate (1:1,v/v). After the completion of the reaction, the reaction mixture wascooled to room temperature and evaporated under reduced pressure.The residue was partitioned between water (50 mL) and dichloromethane (50 mL), and the water phase was extracted twoadditional times with the same volume of dichloromethane. Thecombined organic phases were washed with water and brine andevaporated under reduced pressure. The crude product was crystallizedfrom petroleum ether/ethylacetate (3:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 5%-palladium/activated carbon; hydrogen; In methanol; under 760.051 Torr; | General procedure: The crude nitroderivative (5) from the previous step(0.75 mmol) was hydrogenated under atmospheric pressure inmethanol (50 mL) with 5% wt. palladium on charcoal (50 mg). Afterthe consumption of hydrogen, the reaction mixture was filteredthrough Celite, washed with methanol and evaporated underreduced pressure. The crude product was dissolved in 2M hydrochloricacid (50 mL) and extracted with dichloromethane (25 mL).The water phase was neutralized with 5% sodium hydrogen carbonate,and the precipitate was filtered off and washed with water.The crude product was dried in a vacuum desiccator and finallypurified by flash column chromatography using mobile phasechloroform/methanol (4:1, v/v). |
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