Structure of Acetopiperone
CAS No.: 3162-29-6
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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. : | 3162-29-6 |
| Formula : | C9H8O3 |
| M.W : | 164.16 |
| SMILES Code : | C1=C(C=CC2=C1OCO2)C(=O)C |
| MDL No. : | MFCD00005831 |
| InChI Key : | BMHMKWXYXFBWMI-UHFFFAOYSA-N |
| Pubchem ID : | 76622 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 12 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.22 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 42.7 |
| TPSA ? Topological Polar Surface Area: Calculated from |
35.53 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.93 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.64 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.62 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.84 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.21 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.45 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.56 |
| Solubility | 4.47 mg/ml ; 0.0272 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-0.96 |
| Solubility | 17.9 mg/ml ; 0.109 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.48 |
| Solubility | 0.547 mg/ml ; 0.00333 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) |
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) |
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 |
-6.85 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) |
1.91 |
* 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 |
|---|---|---|
| 87% | With sodium hydride; In dimethyl sulfoxide; at 15 - 23℃; for 16h;Inert atmosphere; | A dry, 500-mL, three-necked flask is fitted with a Teflon-coated magnetic stirring bar, a rubber septum, a thermometer, and a reflux condenser to which is attached a T-tube connected to a source of pure nitrogen. The remaining joint of the T-tube is connected to a bubbling device so that the rate of nitrogen flow can be observed throughout of the reaction. The apparatus is arranged so that the flask may be cooled intermittently with a water bath. After the reaction vessel has been flushed with nitrogen a static nitrogen atmosphere is maintained in the reaction vessel for the remainder of the reaction. The flask is charged with ca. 60% dispersion of sodium hydride (5 g, 0.125 mole) in mineral oil (Note 1). The mineral oil is washed from the hydride with petroleum benzine 40/60 (3 x 40 ml.) (Note 2). The supernatant petroleum benzine layer is removed using a Luer-lock hypodermic syringe with a stainless-steel needle inserted through the rubber septum. The residual sodium hydride is mixed with 80 ml_ of dimethyl sulfoxide (Note 3), and the rubber septum is replaced with a pressure-equalizing dropping funnel. A solution of 16.4 g (0.1 mole) of 1-(1 ,3-benzodioxol-5- yl)ethanone (Note 4) and 26.9 g (0.125 mole) of <strong>[618-89-3]methyl 3-bromobenzoate</strong> (Note 5) in 60 mL of dimethyl sulfoxide is placed in the dropping funnel. The funnel is stoppered, stirring is begun and the contents of the flask are cooled in a water bath to 15 0C. The solution of 1- (1 ,3-benzodioxol-5-yl)ethanone and <strong>[618-89-3]methyl 3-bromobenzoate</strong> is added slowly so that hydrogen evolution is maintained at the controllable rate and the temperature did not rise above 20 0C over a period of 60 minutes (Note 6). After the addition is completed, the bath is removed, and the reaction mixture is stirred at room temperature (23 0C) for 15 hours. The resulting red-brown homogeneous reaction mixture is poured slowly into 500 mL of an ice and water containing 5 mL of 85% orthophosphoric acid (Note 7) with stirring. After 1 hour stirring the product is removed by filtration (Note 8), washed by suction filtration with water (2 x 100 mL), and vacuum dried to constant weight at 40 0C for 6 hours to give 34.4 g of the crude (Note 9) product. Recrystallization from 200 mL of 99.9% ethanol and 200 mL ethyl acetate (Note 10) and drying in vacuum to constant weight at 40 C for 6 hours gives 28.5 g (82% yield) of pure (Note 11) 1-(1 ,3-benzodioxol-5-yl)-3-(3-bromophenyl)propane-1 ,3-dione, m.p. 136-137 0C. The filtrate is concentrated under reduced pressure to a volume ca. 30 mL, the crystalline solid that separates is collected on a filter, washed by suction filtration with ethanol (2 x 10 mL) and vacuum dried to constant weight at 40 0C for 6 hours, yielding an additional crop (3.15 g) of the crude product. The crude product is recrystallized twice from 20 mL of 99.9% ethanol and 20 mL ethyl acetate and vacuum dried to constant weight at 40 CC for 6 hours to afford additional 1.8 g (5% yield) of pure 1-(1 ,3-benzodioxol-5-yl)-3-(3- bromophenyl)propane-1 ,3-dione (Note 12). The total yield of the product is 30.3 g (87%).2. Notes1. Sodium hydride, 57-63% oil dispersion, order number 13431 available from Alfa Aesar GmbH & Co KG, Karlsruhe was used. 2. Petroleum benzine GR for analysis boiling range 40-60 0C, order number 101775 from Merck KGaA, Darmstadt was used.3. The dimethyl sulfoxide GR for analysis, order number 102952 from Merck KGaA, Darmstadt was used without further purification. 4. 1-(1 ,3-Benzodioxol-5-yl)ethanone, 98%, order number A13597 available from Alfa Aesar GmbH & Co KG, Karlsruhe was used.5. Methyl 3-bromobenzoate, 98%+, order number A16174 available from Alfa Aesar GmbH & Co KG, Karlsruhe was used.6. A foaming is observed during the addition of the solution. The usage of mechanical stirrer and an antifoaming agent like polyethylene glycol dimethyl ether may be necessary at the upscaling.7. The orthophosphoric acid, 85% w/w aq. solution, GR for analysis, order number 100573 from Merck KGaA, Darmstadt was used.8. The pH-value of the reaction mixture is pH = 7. By acidification with additionally 15 ml_ ortophosphoric acid to pH = 2, 1.3 g of 3-bromobenzoic acid may be obtained.9. Purity of the product determined by HPLC is 96.3%.10. The ethanol 99.9% absolute GR for analysis, order number 100983, and ethyl acetate GR for analysis, order number 109623 available from Merck KGaA, Darmstadt was used. 1 1. Purity of the product determined by HPLC is 99.3%. Analytical HPLC is performed by using a Waters HPLC system with a Waters 996 Photodiode Array Detector. All separations involved a mobile phase of 0.1% v/v trifluoroacetic acid (TFA) in water (solvent A) and 0.1% v/v TFA in acetonitrile (solvent B) by using a reversed phase (RP) column Eurospher RP 18, 100 A, 5 μm, 250 x 4.6 mm at flow rates of 1 mL/min. The compound is dissolved in acetonitrile GR for HPLC at a concentration 1 mg/mL. Peaks with retention times (RT) 20.9 and 10.3 min are enol and keto forms respectively ... |

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