Structure of 6272-26-0
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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. : | 6272-26-0 |
Formula : | C8H6O3 |
M.W : | 150.13 |
SMILES Code : | O=C1COC2=CC(O)=CC=C12 |
MDL No. : | MFCD00068174 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.3 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.88 |
Solubility | 1.98 mg/ml ; 0.0132 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.69 |
Solubility | 3.06 mg/ml ; 0.0204 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.98 |
Solubility | 1.56 mg/ml ; 0.0104 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 |
-6.42 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 |
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) |
1.8 |
* 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 |
---|---|---|
92% | With ammonium chloride;palladium dihydroxide; In tetrahydrofuran; hydrogenchloride; methanol; ethyl acetate; | Preparation 3 2,3-Dihydro-benzofuran-6-ol 6-Hydroxy-2H-benzofuran-3-one (3 g) was suspended in anhydrous tetrahydrofuran under an argon atmosphere and cooled to 0° C. Lithium aluminium hydride (20 ml of a 1M solution in tetrahydrofuran) was added dropwise over 10 min and the reaction allowed to reach room temperature over 2 hours. The reaction was cooled to 0° C. and treated dropwise with saturated ammonium chloride solution. Ethyl acetate (200 ml) was added and the mixture filtered through Celite. The ethyl acetate layer was separated, dried (MgSO4) and evaporated to dryness under reduced pressure. The resulting mixture of 2,3-dihydro-benzofuran-3,6-diol and benzofuran-6-ol (approximately 1:1 by 250 MHz 1H NMR) was dissolved in a mixture of hydrochloric acid (200 ml, 5M aqueous solution) and methanol (300 ml) and palladium hydroxide (0.5 g) added. The mixture was stirred under a hydrogen atmosphere for 3 hours then filtered through Celite. The organics were removed by evaporation under reduced pressure and the resulting solution neutralised with concentrated anmmonia solution. The product was extracted into dichloromethane. The dichloromethane solution was dried (MgSO4) and evaporated to dryness under reduced pressure to yield the title compound (2.5 g, 92percent). 1H NMR (250 MHz, CDCl3) delta: 3.11 (2H, t, J=8.4 Hz), 4.57 (2H, t, J=8.4 Hz), 6.27-6.34 (2H, m), 6.92-7.02 (1H, m); m/z (API+): 139.1 (M+3H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In methanol; | EXAMPLE 17 Synthesis of 2-[(3-ethoxy-4-benzyloxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and <strong>[60186-33-6]3-ethoxy-4-benzyloxybenzaldehyde</strong> 1.80 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60 C. for four hours under reduced pressure to obtain the desired compound 1.33 g. FAB MASS; 389 (M+1) 1H-NMR (ppm, in DMSO-d6); 1.34 (3H, t), 4.08 (3H, s), 5.14 (2H, s), 6.70-6.73 (3H, m), 6.79 (1H, s), 7.08 (1H, d, J=8.5 Hz), 7.39-7.60 (8H, m), 11.11 (1H, s) |
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