Structure of 159184-14-2
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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. : | 159184-14-2 |
Formula : | C13H18N2O5 |
M.W : | 282.29 |
SMILES Code : | O=C(OC(C)(C)C)NCCOC1=CC=C([N+]([O-])=O)C=C1 |
MDL No. : | MFCD26743665 |
InChI Key : | LDOYKECYRDLCDM-UHFFFAOYSA-N |
Pubchem ID : | 18173671 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 8 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 75.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
93.38 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.53 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.5 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.1 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.81 |
Solubility | 0.438 mg/ml ; 0.00155 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.02 |
Solubility | 0.0267 mg/ml ; 0.0000948 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.28 |
Solubility | 0.15 mg/ml ; 0.00053 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
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 |
-6.3 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 |
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) |
2.5 |
* 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 |
---|---|---|
a 4-[2-(tert.butyloxycarbonylamino)ethoxy]-nitrobenzene Prepared analogously to the compound of Example Va), Rf value: 0.18 (Reversed Phase silica gel; methanol/5% saline solution=6:4) | ||
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 30.0h;Inert atmosphere; | General procedure: Step 4: Preparation of [3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester (RO4515815-002) To a solution of (3-hydroxy-propyl)-carbamic acid tert-butyl ester (7.03 g, 40.1 mmol) in anhydrous THF (40 mL) were added 4-nitrophenol (5.07 g, 36.5 mmol), triphenylphosphine (10.5 g, 40.1 mmol) at room temperature under nitrogen atmosphere. The resulting solution was cooled to ?0 C. with an ice-water bath and then diisopropyl azodicarboxylate (DIAD, 8.1 g, 40.1 mmol) was added drop-wise for 15-20 minutes. After addition, the solution was warmed to room temperature and stirred for 15 h at which time LCMS analysis indicated the presence of 16% of the starting material. Then, another 0.1 equivalents of all the above reagents were added and the reaction mixture was stirred for another 15 h. The solids were filtered off and were washed with ethyl acetate and then the filtrate was washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. Filtration and concentration gave the crude residue which was purified using an ISCO (340 g) column chromatography to obtain [3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester (64% yield) as a white solid. ES(+)-HRMS m/e calcd. for C14H20N2O5 (M+Na)+ 319.1264, obsd. 319.1266. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium formate;palladium; In ethanol; | Step E. tert-Butyl 2-(4-aminophenoxy)ethylcarbamate <strong>[159184-14-2]tert-Butyl 2-(4-nitrophenoxy)ethylcarbamate</strong> (6.87 g, 24.34 mmol) was dissolved in ethanol, 10% palladium on carbon (1.0 g) was added followed by ammonium formate (7.7 g, 122 mmol). The solution was heated to reflux for 0.5 hours. The mixture was cooled to ambient temperature, filtered through a Celite pad and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel Merck-60 (eluant: 1:1 hexane-ethyl acetate). The solvent was removed in vacuo to furnish the title compound (4.94 g, 19.58 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; hexane; ethyl acetate; | (1-1) 4-Nitrophenol (4.01 g), 2-(tert-butoxycarbonylamino)ethanol (4.65 g) and triphenylphosphine (7.55 g) were dissolved into tetrahydrofuran (50 ml) and the solution was ice cooled. Azo dicarboxylic acid diethyl (5.52 g) dissolved in tetrahydrofuran (5 ml) was added drop-wise into the ice-cooled solution. After being stirred for one hour at room temperature, the reaction mixture was concentrated under vacuum. Residue was dissolved into ethyl acetate (50 ml). Hexane (400 ml) was added to the ethyl acetate solution and insoluble matter formed was removed from solution by filtration. Filtrate was concentrated under vacuum to small volume. Concentrate was purified by silica-gel column chromatography using ethyl acetate:hexane (1:1) as the solvent system to obtain N-(tert-butoxycarbonyl)-2-(4-nitrophenoxy)ethylamine (5.91 g) as color-less oily substance. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; | EXAMPLE 215 STR104 2-(4-Nitrophenoxy)ethylcarbamic acid 1,1-dimethylethyl ester A solution of 480 mg (2.79 mmol) of amine from Example 214 in 20 mL of methylene chloride was treated with 610 mg (2.80 mmol) of di-tert-butyl dicarbonate. After stirring at room temperature for 40 min., the reaction mixture was concentrated and the resulting yellow solid was used for the next step without further purification: 1H NMR (200 MHz, CDCl3) delta8.15 (d, 2H, J=9Hz), 6.90 (d, 2H, J=9Hz), 4.94 (bs, 1 H, N-H), 4.05 (bt, 2H, J=5.0Hz), 3.50 (q, 2H, J=5.0Hz). |
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