Structure of 406482-72-2
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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. : | 406482-72-2 |
Formula : | C19H20BNO2 |
M.W : | 305.18 |
SMILES Code : | N#CC1=CC=C(C2=CC=C(B3OC(C)(C)C(C)(C)O3)C=C2)C=C1 |
MDL No. : | MFCD17015781 |
InChI Key : | UQGDIRDLIFFOHN-UHFFFAOYSA-N |
Pubchem ID : | 11822881 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 23 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.32 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 93.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.28 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.66 |
Solubility | 0.00662 mg/ml ; 0.0000217 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.85 |
Solubility | 0.00432 mg/ml ; 0.0000142 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.59 |
Solubility | 0.0000792 mg/ml ; 0.000000259 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) |
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) |
Yes |
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 |
-5.14 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 |
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) |
3.29 |
* 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 |
---|---|---|
94% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 16h;Inert atmosphere; Reflux; | A flask was flushed with nitrogen and charged with 6 2-chloro-4-phenyl-6-(3-(9-phenyl-9H-fluoren-9-yl)phenyl)-1,3,5-triazine (10 g, 19.7 mmol), 28 4?-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1?-biphenyl]-4-carbonitrile (6.6 g, 21.7 mmol), 8 Pd(PPh3)4 (0.46 g, 0.39 mmol), and 9 K2CO3 (5.4 g, 39.4 mmol). A mixture of deaerated 10 THF/11 water (13:1, 270 mL) was added and the reaction mixture was heated to reflux under a nitrogen atmosphere for 16 h. After cooling down to room temperature, the THF was removed in vacuo, 12 dichloromethane was added and the organic phase was washed with water three times. Subsequently, the organic phase was dried over Na2SO4 and filtered over a pad of silica. After rinsing with additional dichloromethane, the colorless filtrate was concentrated and 14 n-hexane was added. After stirring for 1 h, the precipitate was collected by suction filtration and washed with n-hexane to yield 12.1 g (94%) of a white solid after drying. Final purification was achieved by sublimation. m/z=651 ([M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium phosphate; In tetrahydrofuran; water; at 45℃; for 18h;Inert atmosphere; | Example of reaction conditions which can be suitably used for preparation of compound of Formula CO from compound of Formula 2 Potassium phosphate K3PO4 (as 10m L aqueous solution, 2 eq.) was degassed with nitrogen for 30 min. THE (41 ml) was also degassed with nitrogen for 30 min. The THF flask was then charged with previously synthesized intermediate of formula 2 (4.5 g, ieq.), 4'-(4,4,5 ,5-tetramethyl-i, 3,2 -dioxaborolan-2 -yl) -[1,1 -biphenyl] -4-carbonitrile (0268) [406482-72-2] (l.ieq.), and palladium source Pdi72 [CAS 1798781-99-3] (0.02 eq.) under a positive nitrogen pressure. The degassed potassium phosphate solution was added, nitrogen purged reflux condenser was attached to the flask and a reaction mixture heated to 45 C with stirring for 18 h. The mixture was allowed to cool down to the room temperature. The precipitate was filtered, washed thoroughly with water. After dissolution in refluxing chlorobenzene and filtration on silicagel layer, the reduction of the solvent afforded white powder that was recrystallzed in loomL chlorobenzene to afford 4.yg (82%) product, m/z 663 [M+H]+. |