Structure of 167415-27-2
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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. : | 167415-27-2 |
Formula : | C6H2BrF2NO2 |
M.W : | 237.99 |
SMILES Code : | C1=C(F)C(=CC(=C1[N+](=O)[O-])F)Br |
MDL No. : | MFCD00042184 |
Boiling Point : | No data available |
InChI Key : | GJFYMYJYPARISZ-UHFFFAOYSA-N |
Pubchem ID : | 2736286 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.88 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
Solubility | 0.124 mg/ml ; 0.000522 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.25 |
Solubility | 0.133 mg/ml ; 0.000559 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.19 |
Solubility | 0.152 mg/ml ; 0.000638 mol/l |
Class? Solubility class: Log S scale |
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) |
No |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.88 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 |
3.0 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) |
2.04 |
* 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 |
---|---|---|
84.4% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; benzene; for 12h;Heating / reflux; | (7-a) Synthesis of compound 2,5-difluoro-4-nitro-4'-(trans-4-pentylcyclohexyl)biphenyl represented by formula: First, 50 ml of ethanol containing 7.52 g of <strong>[143651-26-7]4-(trans-4-pentylcyclohexyl)phenylboronic acid</strong> dissolved therein, 50 ml of benzene containing 5.0 g of 4-bromo-2,5-difluoro-1-nitrobenzene dissolved therein, 21.0 ml of a sodium carbonate aqueous solution with a concentration of 2.0 mol/l, and 0.61 g of tetrakis(triphenylphosphine)palladium(0) were put in an argon-replaced 200 ml flask, and stirred under reflux for 12 hours.. After the reaction, water and ether were added to the reaction solution for extraction.. The resultant ether layer was washed with a saturated brine and dried with sodium:sulfate.. The solvent was then distilled off.. The residue was purified by silica gel column chromatography (eluent:toluene/hexane=1/4) and recrystallized from hexane, to obtain 6.87 g (Y: 84.4%) of 2,5-difluoro-4-nitro-4'-(trans-4-pentylcyclohexyl)biphenyl.. The purity of the resultant compound was 100.0% as measured by GC. The phase transfer temperature of the compound was as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a mixture of <strong>[33689-29-1]methyl 1-hydroxycyclopropanecarboxylate</strong> (Aldrich) (1.0 g, 8.8 mmol) and 15-crown-5 (cat. amount) in THF (30 ml) was added NaH (400 mg, 10 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 min and then added 1-bromo-2,5-difluoro-4-nitrobenzene (Aldrich) (2 g, 8.4 mmol). The mixture was stirred at room temperature for additional 16 hrs. When TLC indicated the reaction was completed, the reaction mixture was quenched with saturated NH4Cl aqueous solution. After removal of the organic solvent, the mixture was extracted with ethyl acetate (*3). The combined organic phases were washed with brine (*3), dried over anhydrous Magnesium sulfate and filtered. The filtration was concentrated under reduced pressure to give the crude product, which was purified by flash column chromatography on silica gel using a gradient 0-10% ethyl acetate in hexanes to afford the title compound as yellow solid. LC-MS: Rt=1.43 mins; MS m/z [M+H]+ 333.9; Method 5-95AB 1.5minLC_v003 1H NMR (400 MHz, CDCl3) delta 8.15 (1H, d), 6.98 (1H, d), 3.57 (3H, s), 1.38 (2H, m), 1.18 (2H, m). | ||
Step 1 : methyl 1-(5-bromo-4-fluoro-2-nitrophenoxy)cvclopropanecarboxylate: To a mixture of <strong>[33689-29-1]methyl 1-hydroxycyclopropanecarboxylate</strong> (Aldrich) (1.0 g, 8.8 mmol) and 15- crown-5 (cat. amount) in THF (30 ml) was added NaH (400 mg, 10 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 min and then added 1-bromo-2,5- difluoro-4-nitrobenzene (Aldrich) (2 g, 8.4 mmol). The mixture was stirred at room temperature for additional 16 hrs. When TLC indicated the reaction was completed, the reaction mixture was quenched with saturated NH4CI aqueous solution. After removal of the organic solvent, the mixture was extracted with ethyl acetate (x3). The combined organic phases were washed with brine (x3), dried over anhydrous Magnesium sulfate and filtered. The filtration was concentrated under reduced pressure to give the crude product, which was purified by flash column chromatography on silica gel using a gradient 0-10% ethyl acetate in hexanes to afford the title compound as yellow solid. LC-MS: Rt=1.43 mins; MS m/z [M+H]+ 333.9; Method 5-95AB 1.5minLC_v003 1H NMR (400 MHz, CDCI3) delta 8.15 (1 H, d), 6.98 (1 H, d), 3.57 (3H, s), 1.38 (2H, m), 1.18 (2H, m). |
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