Structure of 60758-86-3
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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. : | 60758-86-3 |
Formula : | C10H11NO2 |
M.W : | 177.20 |
SMILES Code : | N#CC1=CC=C(OC)C(OCC)=C1 |
MDL No. : | MFCD02256160 |
InChI Key : | XTIINWPNAMHVDG-UHFFFAOYSA-N |
Pubchem ID : | 3934769 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.95 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.89 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.27 |
Solubility | 0.945 mg/ml ; 0.00533 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.4 |
Solubility | 0.706 mg/ml ; 0.00398 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.14 |
Solubility | 0.128 mg/ml ; 0.000723 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 |
-6.04 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) |
1.72 |
* 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 |
---|---|---|
76.1% | Dimethylsulfone (191. Ig, 2.03 moles, from Aldrich Chemicals, Milwaukee, WI) and tetrahydrofuran (1.65 L, from Aldrich Chemicals, Milwaukee, WI) were charged to a 12 L three-necked flask at room temperature. The mixture was cooled to 0-5C. n-BuLi (750 ml of 2.5M solution in hexanes, from Aldrich Chemicals, Milwaukee, WI) was added to the flask at a rate such that the reaction mixture was maintained at 0-5C. A line rinse with 150 ml tetrahydrofuran followed. The mixture was stirred at 0-5C for 60-70 minutes. 3-ethoxy-4- methoxybenzonitrile (300.0 g, 1.69 moles, in 750 ml tetrahydrofuran) was then charged to the flask at a rate such that the reaction mixture was maintained at 0-5 C . A line rinse with 300 ml tetrahydrofuran followed. The mixture was stirred at 0-5C for another 10-15 minutes. After warming to room temperature, the reaction mixture was stirred at room temperature for 1.5-2 hours, while purged with nitrogen. NaBH4 (83.1 g, 2.20 moles, from Aldrich Chemicals, Milwaukee, WI) and 150 ml of tetrahydrofuran were then charged to the reaction mixture. The reaction mixture was stirred at 0-50C for 15-30 minutes. HOAc (450 ml, 7.83 moles, from Fisher Scientific, Pittsburgh, PA) was charged to the flask at a rate such that the reaction mixture was maintained at 0-50C. The mixture was stirred at 0-50C for an additional 2-3 hours. The mixture was then charged with 2.25 L of NaOH (2.5N, pH 12 to 13, from Fisher Scientific, Pittsburgh, PA), and stirred at 0-50C for another 15-30 minutes. After warming to room temperature, the reaction mixture was heated to reflux at about 600C. After reflux for 12-14 hours, the mixture was cooled to 35-40C, and 3.0 L of water was added. The mixture was further cooled to 0-5C over a period of 1.5-2 hours. The mixture was filtered under vacuum, and the filtered solid was washed with 2 L of deionized water. The solid was dried in a tray at 50-550C under vacuum. The yield of 2-(3-ethoxy-4-methoxyphenyl)-l-(methanesulfonyl)-eth- 2-ylamine was found to be 352 g (76.1%) based on a 300 g input of 3-ethoxy-4- methoxybenzonitrile (HPLC indicated 99.74% purity by peak area). | |
65% | In a flask, 5 litres of tetrahydrofuran was charged followed by 1.06 kg of dimethylsulfone. This reaction mass was cooled for 25 to 30 minutes at 0C. Aftercooling, 1M potassium-hexamethyldisilazane was added followed by 10 litres of tetrahydrofuran. The reaction mass was stirred for an hour at 0 to 10 C. After stirring, 1 kg of 3-ethoxy-4-methoxybenzonitrile was dissolved in 2 litres tetrahydrofuran and was added to the above reaction mass. The reaction mass was stirred for 30 minutes and cooled. After cooling, 0.433 kg of sodium borohydride was added followed bytetrahydrofuran and 5 litres of acetic acid and the total reaction mass was stirred for 3- 4 hours at 0 to 10 C. After completion of reaction, sodium hydroxide solution was added to it and stirred for 45 minutes. The reaction mass was warmed and further heated for 3 to 4 hours at 60 to 65C. After completion of reaction, the reaction solution was allowed to cool to room temperature for half an hour. The layers were separated. The combinedorganic layer was treated with aq. HC1 and water was added to the concentrated mass. The aqueous layer was treated with ethyl acetate. Finally sodium hydroxide solution was added to the aqueous layer and solid was precipitated. The solid was filtered, washed with water and dried at 50C and further 1.0 kg (65%) of material was unloaded. | |
50% | Dimethyl sulfone (0.639 g, 0.067 mmoles) was added to dimethylsulfoxide (10 ml) and stirred at room temperature for 5-10 minutes. Potassium tertiary butoxide (1.89 g, 0.169 mmoles) was added slowly to the reaction mixture at 30C and stirred for three hours. 3-ethoxy-4-methoxy benzonitrile (1.0 g, 0.056 mmoles) in tetrahydrofuran (2 ml) was added to the reaction mixture over a period of 30 minutes and was stirred for three hours at room temperature. Sodium borohydride (0.213 g,0.056 mmoles) was added to the reaction mixture at 30 C and maintained for one hour. Ammonium chloride (10 ml) was added to the reaction mixture and extracted with ethyl acetate (20 ml). The ethyl acetate layer was washed with water (10 ml). The ethyl acetate layer was distilled at 30 C to provide crude compound. The crude compound was washed with methyl tertiary butyl ether to provide the title compound as pale yellow colored solid.Yield: 750 mg (50%) |
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