Structure of 1481-57-8
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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. : | 1481-57-8 |
Formula : | C6HBr2F2NO2 |
M.W : | 316.88 |
SMILES Code : | [O-][N+](=O)C1=C(F)C(F)=CC(Br)=C1Br |
MDL No. : | MFCD11226312 |
InChI Key : | QRVCXRRZIUMPII-UHFFFAOYSA-N |
Pubchem ID : | 223075 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
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 | 50.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.59 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.18 |
Solubility | 0.021 mg/ml ; 0.0000664 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.97 |
Solubility | 0.034 mg/ml ; 0.000107 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.02 |
Solubility | 0.0302 mg/ml ; 0.0000953 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) |
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 |
-5.87 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.28 |
* 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 |
---|---|---|
93% | With palladium 10% on activated carbon; hydrogen; triethylamine; In methanol; at 50℃; for 2.5h; | First, 0.638 g (2.01 mmol) of <strong>[1481-57-8]1,2-dibromo-4,5-difluoro-3-nitrobenzene</strong> was dissolved in 4 mL of methanol, and then 48.4 mg of 10% Pd/C (50% wet) and 6.2 mg (0.06 mmol) of triethylamine were added. The atmosphere inside the reaction vessel was substituted with hydrogen, and the reaction mixture was reacted at 50C for 2 hours under slight hydrogen pressurization. Analysis of the resulting reaction product by HPLC revealed 2.2 area% of 2,3-dibromo-5,6-difluoroaniline as a residual intermediate. Reaction was continued under the same conditions for a further 0.5 hours. The catalyst was then removed by filtration. The resulting liquid was subjected to quantitative analysis by HPLC. The yield of 2,3-difluoroaniline was 93%. The intermediate 2,3-dibromo-5,6-difluoroaniline had been eliminated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sulfuric acid; nitric acid; In water; at 20 - 35℃; for 1.5h; | First, 8 mL of 30% by mass fuming sulfuric acid was cooled to 5C, and 1.45 g of 65% nitric acid (equivalent to 15 mmol of nitric acid) was then added gradually. Following completion of the addition, the temperature was raised to room temperature, and after stirring for 5 minutes, 2.71 g (10 mmol) of 1,2-dibromo-4,5-difluorobenzene was added. The temperature of the reaction mixture was raised to 35C, the mixture was stirred for 1 hour 30 minutes, and the temperature was then cooled to room temperature. The reaction mixture was poured onto ice, and the product was extracted with ethyl acetate. The resulting ethyl acetate solution was washed twice with water, and then with a saturated aqueous solution of sodium bicarbonate and a saturated saline solution, before being dried over magnesium sulfate. The magnesium sulfate was then removed by filtration, and quantitative analysis of the resulting solution by HPLC revealed a reaction yield of 94% of the target product 1,2-dibromo-4,5-difluoro-3-nitrobenzene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With ethanol; water; iron; calcium chloride; at 55℃; for 3.2h; | First, 1.57 g (4.95 mmol) of <strong>[1481-57-8]1,2-dibromo-4,5-difluoro-3-nitrobenzene</strong> was dissolved in a mixed solution of 5 mL of ethanol and 2.5 mL of water, and 0.85 g (15.2 mmol) of iron powder and 0.54 g (4.87 mmol) of calcium chloride were then added to the solution. The resulting mixture was heated to 55C and stirred for 3.2 hours. The mixture was then filtered, and the resulting filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography, yielding 1.25 g (yield: 88%) of skin-colored crystals of 2,3-dibromo-5,6-difluoroaniline. (0069) 2,3-dibromo-5,6-difluoroaniline: 1H-NMR (400 MHz, CDCl3): delta 6.91 (dd, 1H), 4.45 (brs, 2H) |
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