Structure of 19677-37-3
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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. : | 19677-37-3 |
Formula : | C13H15ClO4 |
M.W : | 270.71 |
SMILES Code : | O=C(OCC)C(C1=CC=C(Cl)C=C1)C(OCC)=O |
MDL No. : | MFCD06204602 |
InChI Key : | PPESOPZGUSEQSO-UHFFFAOYSA-N |
Pubchem ID : | 267418 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.38 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 67.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.21 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.66 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.31 |
Solubility | 0.132 mg/ml ; 0.000487 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.97 |
Solubility | 0.0293 mg/ml ; 0.000108 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.03 |
Solubility | 0.0256 mg/ml ; 0.0000944 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
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 |
-5.69 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.13 |
* 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 |
---|---|---|
85% | With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 25 h; | EXAMPLE 6 Coupling of 4-chlorobromobenzene with diethyl malonate to give diethyl 2-(4-chlorophenyl) malonate 191.5 mg of 4-chlorobromobenzene (1 mmol) and 160 mg of diethyl malonate (1 mmol) were dissolved in 5 ml of N,N-dimethylformamide under protective gas, admixed with 652 mg of cesium carbonate (2 mmol) and stirred for 1 h. 17.9 mg (4 mol percent) of the HBPNS ligand and 9.0 mg of palladium(II) acetate (4 mol percent) were then added, and the mixture was heated to 80° C. for 24 h. For workup, 5 ml of water and 10 ml of toluene were added, the mixture was shaken, and the lower water phase was discharged and washed once again with 5 ml of water to remove residual dimethylformamide. After removal of the toluene on a rotary evaporator, 230 mg (0.85 mmol, 85percent) of the product were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With cesium acetate; copper(II) bis(trifluoromethanesulfonate); triethylamine In 1,2-dichloro-ethane at 30℃; for 48 h; Sealed tube | General procedure: In an atmosphere controlled glovebox, Cu(OTf)2 (398 mg, 1.10 mmol, 2.20 equiv.), arylboroxine (0.330 mmol, 0.670 equiv.), and CsOAc (106 mg, 0.550 mmol, 1.10 equiv.) were added sequentially to a 2 dram vial charged with a stir bar. The sp3-carbon nucleophile (0.500 mmol, 1.00 equiv.) and triethylamine (0.210 mL, 1.50 mmol, 3.00 equiv.) were added as a solution in anhydrous 1,2-DCE (1.20 mL). Additional 1,2-DCE (2×0.5 mL) was used to quantitatively transfer the solution to the reaction mixture. The vial was sealed with a PTFE-lined cap and stirred outside the glovebox at 30° C. Reaction progress was generally monitored by GC-FID using n-dodecane as an internal standard. Unless otherwise noted, reactions were quenched after 36-48 hours, when >95percent conversion of sp3-carbon nucleophile was reached. The reaction was quenched with 5 mL of brine and extracted with EtOAc (4×10 mL). The organic layer was then washed with 5 mL brine and dried with Na2SO4, and the solvent was removed by vacuum. The crude residue was purified by flash silica gel chromatography. Note: the order of addition of reagents is important for achieving optimal yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5 h; Stage #2: at -78 - 20℃; |
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 °C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 °C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4percent ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81percent yield) as a colorless liquid. |
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