Structure of 1951-36-6
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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. : | 1951-36-6 |
Formula : | C8H6O4 |
M.W : | 166.13 |
SMILES Code : | O=CC1=CC(O)=C(C=O)C=C1O |
MDL No. : | MFCD22055335 |
InChI Key : | PIWMYUGNZBJTID-UHFFFAOYSA-N |
Pubchem ID : | 11084236 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.26 |
TPSA ? Topological Polar Surface Area: Calculated from |
74.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.24 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.64 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.89 |
Solubility | 2.14 mg/ml ; 0.0129 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.4 |
Solubility | 0.654 mg/ml ; 0.00394 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.14 |
Solubility | 12.1 mg/ml ; 0.0729 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 |
No |
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 |
-6.43 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 |
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 |
2.0 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) |
1.0 |
* 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 |
---|---|---|
96% | With boron tribromide; In dichloromethane; at 0 - 20℃;Inert atmosphere; | To a solution of 4 (1.0 g) in dry DCM (150 mL), BBr3(2.0 mL) in 50 mL of CH2Cl2 was added dropwise at 0 C under N2 atmosphere. After being stirred overnight at room temperature, the mixture was cooled to 0 C and water (20 mL) was added in drops to quench the reaction. The residue was extracted with CH2Cl2, washed with brine, dried over MgSO4, and evaporated under reduced pressure, giving the crude compound which was purified by flash chromatography with hexane/ethyl acetate (5:1) as eluent to afford the title compound as an orange solid. Yield: 0.83 g (96%).1H NMR (400 MHz, d6-DMSO, 298K, TMS) delta10.30 (d, 4H, J=8.8 Hz), 7.23 (s, 2H). 13CNMR (100 MHz, d6-DMSO, 298K, TMS) 190.66, 153.25, 128.13, 115.56 ppm. |
94% | With boron tribromide; In dichloromethane; at -40 - 25℃; for 3h;Inert atmosphere; | A three-necked reactor equipped with a thermometer was charged with 3.32 g (17.10 mmol) of the intermediate A synthesized in the step 1 and 160 ml of dichloromethane under a nitrogen stream to prepare a solution, which was cooled to -40 C. After the addition of 51.3 ml (51.29 mmol) of boron tribromide (17% dichloromethane solution) dropwise to the solution, the mixture was stirred at -40 C. for 1 hour. The reaction mixture was then heated to 25 C., and stirred for 2 hours. 600 ml of ice water was added to the reaction mixture, followed by extraction twice with 500 ml of ethyl acetate. The organic layer was collected, and dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. The solvent was evaporated from the filtrate under reduced pressure using a rotary evaporator. The resulting solid was added to 100 ml of toluene. After stirring the mixture for 5 minutes, the resulting crystals were filtered off to obtain 2.67 g of an intermediate B as yellow crystals (yield: 94%). The structure of the target product was identified by 1H-NMR. 1H-NMR (500 MHz, CDCl3, TMS, delta ppm): 10.23 (s, 2H), 9.96 (s, 2H), 7.24 (s, 2H). |
70% | With boron tribromide; In chlorobenzene; | (1) Synthesis of 2,5-dihydroxybenzene-1,4-dicarboaldehyde (AD) 0.5 g of 2,5-dimethoxybenzene-1,4-dicarboaldehyde (AD) and 25 mL of boron tribromide were dissolved in 150 mL of chlorobenzene and stirred at room temperature for 12 hours. After complete reaction, the reacted mixture was neutralized with sodium carbonate, followed by extraction with water and dichloromethane and recrystallization within dichloromethane, thereby obtaining 2,5-dihydroxybenzene-1,4-dicarboaldehyde. The obtained product exhibited yield, property and NMR analysis result as follows. 70% Yield, Yellow crystal, H-NMR (300 MHz, DMSO, TMS): delta=10.30 (s, 2H), 7.20 (s, 2H; aromatic) |
68% | With boron tribromide; In dichloromethane; at 0℃; for 3h;Inert atmosphere; | To a solution of 1-2 <strong>[7310-97-6]2,5-dimethoxyterephthalaldehyde</strong> (6.59 g, 33.93 mmol, 1 eq) in distilled DOM (156 mL) was added at 000 BBr3 at 1 M in distilled DOM (133.7 mL, 133.7mmol, 4 eq). The mixture was stirred for 3 hour under N2. Distilled water (300 mL) was then added at 0O. The mixture was extracted with hot 0H013 (300 mLx4) and washed with Rochelle?s salt (300 mL) and water (2*300 mL). The organic phase was dried over anhydrous Na2SO4 and filtered. After removing the solvent, the remaining residue was purified by recrystallization in 0H013 to give a yellow solid (3.82 g, 68 %).1H NMR (300 MHz, 0D013) 6 ppm = 10.23 (s, 2 H, OHO), 9.97 (s, 2 H, OH), 7.25 (s, 2 H, Ar) data matched with literature reference |
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