Structure of 4-Phenyl-2-pyrrolidinone
CAS No.: 1198-97-6
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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. : | 1198-97-6 |
Formula : | C10H11NO |
M.W : | 161.20 |
SMILES Code : | C2=C(C1CC(=O)NC1)C=CC=C2 |
MDL No. : | MFCD01687226 |
InChI Key : | HOJZEMQCQRPLQQ-UHFFFAOYSA-N |
Pubchem ID : | 121397 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.1 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.2 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.77 |
Solubility | 2.72 mg/ml ; 0.0168 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.2 |
Solubility | 10.2 mg/ml ; 0.0631 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.21 |
Solubility | 0.101 mg/ml ; 0.000624 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 |
-6.57 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) |
1.55 |
* 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 |
---|---|---|
100% | In toluene; for 5h;Reflux; | General procedure: A suspension of carboxylic acid in toluene was heated to reflux for 5 h. After cooling to roomtemperature, the solvent was evaporated and the pure product was obtained. 1H- and 13C-NMR datafor the compounds ()-2a-c [42], are identical with those described in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | the effect of different organic solvents on the reaction yield:9.6 g (0.06 mol) of 4-phenyl-2-pyrrolidone was dissolved in 100 mL of an organic solvent, and the organic solventIn the case of Table 1, the temperature was lowered to the inner temperature of -10 C, and 13.5 g (0.12 mol) of potassium t-butoxide was added in portions, to continue stirring 2h, cooling to the internal temperature -10 ,A solution of 13.0 g (0.12 mol) of methyl chloroacetate was added dropwise and the reaction was continued at -10 to 0 C2h, the reaction was completed, 160 mL of ethyl acetate, 65 mL of saturated ammonium chloride / 65 mL of water were added, stirred and the layers were stirred,2 ethyl acetate extraction 2 times, the organic layer, saturated ammonium chloride 40mL × 2 washed 2 times, 40mL washed 1, 8g anhydrous magnesium sulfate dryDried for 30 min, filtered to give a pale yellow oil, 4-phenyl-2-pyrrolidone-1-acetate, | |
In tetrahydrofuran; water; mineral oil; | (a) Methyl 2-oxo-4-phenylpyrrolidineacetate A total of 8.4 g. of 57% sodium hydride dispersion in mineral oil is washed successively with 200 ml. portions of toluene to remove the mineral oil. The residual sodium hydride is suspended in 600 ml. of tetrahydrofuran and the suspension is treated portionwise, with stirring, with 32.8 g. of <strong>[1198-97-6]4-phenyl-2-pyrrolidinone</strong> (C.A. 53:4253 g.). Upon completion of the addition, the stirred mixture is heated in the range of 35-65 C. from one to three hours (monitoring hydrogen evolution), followed by the dropwise addition of 21.8 g. of methyl chloroacetate. After stirring for about 16 hours at 55-65 C. to insure completeness of reaction, the mixture is cooled and evaporated at reduced pressure. The residue is mixed with 200 ml. of water and extracted twice with 200 ml. portions of ether. The combined ether extract is dried, evaporated and fractionated at reduced pressure. Methyl 2-oxo-4-phenyl-1-pyrrolidineacetate is obtained as an oil, b.p. 158-159 C./0.15 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
l-fer£-Butoxvcarbonvl-3-phenvl-pvrrolidine; A solution of 4-nitro-3"phenyl-butyric acid methyl ester (4.02 g, 18 mmol) and Raney-Nickel (6 ml, slurry in water) in methanol (30 ml) was stirred under hydrogen atmosphere for 3 hours. After filtration using celite and removal of the solvent under reduced pressure, residue was partitioned between water and ethyl acetate. The organic layer was washed with water and brine, and then dried over sodium sulfate. The solvents were removed under reduced pressure, and the residue was dissolved in toluene (50 ml) and the resulting solution was refluxed for 6 hours. Removal of the204 <n="206"/>solvent afforded crude 4-phenyl-pyrrolidin-2-one. A solution of crude 4-phenyl-pyrrolidin-2-one in tetrahydrofuran (20 ml) was added to a solution of lithium aluminum hydride (1.34 g, 35.3 mmol) and the mixture was refluxed for 6 hours. After quenching the reaction with 20% aqueous sodium hydroxide, a solution of drtert-butyl dicarbonate (4.14 g, 19 mmol) was added and the mixture was stirred for 3 hours. Aqueous citric acid and aqueous potassium hydrogen sulfate was added to acidify the solution, and the solution was extracted with toluene. The organic layer was washed with water, aqueous sodium bicarbonate, brine, and dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified with silica gel column chromatography (eluent. hexane/ethyl acetate = 9/1) to afford l-zter£-butoxycarbonyl;3-phenyl-pyrrolidine (1.84 g, 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium tetrahydroborate; nickel(II) chloride hexahydrate; In ethanol; at 0℃; for 2h; | General procedure: Nitroesters 5a-b (1.0 mmol) and NiCl2*6H2O (10.0 mmol) dissolved in 5 mL of ethanol were added into a round bottom flask. The mixture was submitted to magnetic stirring in an ice bath, followed by the addition of NaBH4 (10.0 mmol), and then it was stirred for 2 h at 0 C. Afterwards, 20 mL of NH4Cl was added into the flask and extracted with CHCl3 (3 × 20.0 mL). The organic phases were combined, dried with MgSO4 anhydrous, filtered through Celite and evaporated under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; carbon dioxide; In methanol;Supercritical conditions; Resolution of racemate; | 4-Phenyl-pyiTolidin-2-one (commercial) was separated by SFC (Chiralpak AD column; eluting with C02/MeOH (0.2% NH4OH) =75/25)) to afford the title compound as the second eluting isomer. |
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