Structure of 3,4-Dihydroquinolin-2(1H)-one
CAS No.: 553-03-7
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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. : | 553-03-7 |
Formula : | C9H9NO |
M.W : | 147.17 |
SMILES Code : | C1=CC=CC2=C1NC(=O)CC2 |
MDL No. : | MFCD00016722 |
InChI Key : | TZOYXRMEFDYWDQ-UHFFFAOYSA-N |
Pubchem ID : | 64796 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H317-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.54 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.1 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.34 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.45 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.0 |
Solubility | 1.47 mg/ml ; 0.00999 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 4.12 mg/ml ; 0.028 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.15 |
Solubility | 0.105 mg/ml ; 0.000714 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 |
-6.25 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) |
1.34 |
* 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 |
---|---|---|
37% | With NaH; In ethyl acetate; N,N-dimethyl-formamide; | EXAMPLE 87 1-(1-Phenethylpiperidin-3-ylmethyl)-3,4-dihydro-1H-quinolin-2-one (130) To a solution of 3,4-dihydro-1H-quinolin-2-one (96 mg, 0.65 mmol) in 1.5 mL of DMF was added NaH (26 mg, 1 eq.). The mixture was stirred at room temperature for 45 min. <strong>[253177-03-6]3-Iodomethylpiperidine-1-carboxylic acid tert-butyl ester</strong> (200 mg, 0.62 mmol) in 0.5 mL of DMF was introduced slowly to the reaction mixture. The reaction was continued for 1 h. at room temperature. The mixture was diluted with 10 mL of EtOAc and washed with aqueous HCl (5%, 5 mL), NaHCO3 (sat., 5 mL), brine (10 mL), and dried over anhydrous sodium sulfate. After the solvent was removed, the remaining oily residue was purified by preparative thin layer chromatography (EtOAc/Hexane, 3:7) to afford 3-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)piperidine-1-carboxylic acid tert-butyl ester (2) as a colorless oil (80 mg, 37%). |
37% | With NaH; In ethyl acetate; N,N-dimethyl-formamide; | EXAMPLE 87 1-(1-phenethylpiperidin-3-ylmethyl)-3,4-dihydro-1H-quinolin-2-one (130) To a solution of 3,4-dihydro-1H-quinolin-2-one (96 mg, 0.65 mmol) in 1.5 mL of DMF was added NaH (26 mg, 1 eq.). The mixture was stirred at room temperature for 45 min. <strong>[253177-03-6]3-Iodomethylpiperidine-1-carboxylic acid tert-butyl ester</strong> (200 mg, 0.62 mmol) in 0.5 mL of DMF was introduced slowly to the reaction mixture. The reaction was continued for 1 h. at room temperature. The mixture was diluted with 10 mL of EtOAc and washed with aqueous HCl (5%, 5 mL), NaHCO3 (sat., 5 mL), brine (10 mL), and dried over anhydrous sodium sulfate. After the solvent was removed, the remaining oily residue was purified by preparative thin layer chromatography (EtOAc/Hexane, 3:7) to afford 3-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)piperidine-1-carboxylic acid tert-butyl ester (2) as a colorless oil (80 mg, 37%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With silver(I) acetate; palladium diacetate; trifluoroacetic acid; at 120℃; for 24h;Sealed tube; Inert atmosphere; Schlenk technique; | General procedure: A seal-tube (15 mL) initially fitted with a septum containing anilide 1 (0.5 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol, 10 mol%), and AgOAc (83.5 mg, 0.5 mmol) was evacuated and purged with N2 three times. TFA (4.0 mL), and ethyl 2-iodoacetate (2a; 160 mg, 0.75 mmol) were added to the system and the reaction mixture was stirred at 120 C for 24 h. The mixture was cooled to r.t. and filtered through a short Celite pad and washed with CH2Cl2 several times. The filtrate was concentrated under vacuum and purified on a silica gel column using hexane/EtOAc as eluent to give the corresponding pure oxindole product 3. |
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