Structure of 53400-41-2
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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. : | 53400-41-2 |
Formula : | C9H9NO |
M.W : | 147.17 |
SMILES Code : | O=C1CCCC2=C1C=CC=N2 |
MDL No. : | MFCD03839916 |
InChI Key : | YHHBKPWMEXGLKE-UHFFFAOYSA-N |
Pubchem ID : | 3016811 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.99 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.53 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.78 |
Solubility | 2.44 mg/ml ; 0.0166 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.21 |
Solubility | 9.12 mg/ml ; 0.062 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.0 |
Solubility | 0.147 mg/ml ; 0.000998 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 |
-6.49 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) |
1.81 |
* 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 |
---|---|---|
90.9% | With sodium tetrahydroborate; In ethanol; at 25℃; for 16h; | 7,8-dihydro-quinoline -5 (6H) - one (2.2g, 14.9mmol) was dissolved in ethanol (20 mL) was added NaBH4 (1.2g, 31.7mmol), 25 reaction was stirred for 16 hours. The reaction mixture was washed with water (30mL) was quenched by adding ethyl acetate (20mL × 3) organic phases spin dry to give the title compound as a white solid (2g, 90.9% yield). |
With sodium tetrahydroborate; In methanol; ethyl acetate; | Step 1. A stirred solution of (5,6,7,8)-tetrahydroquinoline-5-one (500 mg, 3.4 mmol) in MeOH (17 mL) was cooled to 0 C. under Argon and treated with NaBH4 (128.7 mg, 3.4 mmol). The reaction was stirred over 16 h and allowed to warm to ambient temperature. The solvent was removed under reduced pressure and the crude oil was chromatographed on a silica gel column packed in 95:5 EtOAc:hexanes and eluted with same. The appropriate fractions were combined and the solvent was removed under reduced pressure to give the 5-hydroxy-(5,6,7,8)-tetrahydroquinoline. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; In xylene; at 160℃; for 18h; | In a nitrogen atmosphere, 24 mL of malonaldehyde tetraethyl acetal and 7.71 g of ammonium acetate were added in that order to xylene (80 mL) solution of 11.2 g of 1,3-cyclohexadione, and a reflux condenser tube fitted with a Dean-Stark water separator was attached to the reactor, and this was stirred at 160C for 18 hours. The reaction liquid was cooled to room temperature, the solvent was evaporated off under reduced pressure, the residue was extracted with chloroform, and the chloroform layer was washed with saturated saline water and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was separated and purified through silica gel column chromatography (chloroform/methanol = 97/3) to obtain 2.21 g of the entitled compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | toluene-4-sulfonic acid; In N,N-dimethyl-formamide; for 16h;Heating / reflux; | A mixture of 3-aminocyclohex-2-enone (100 mmol), 1 ,1 , 3,3- tetraethoxypropane (1 10 mmol), and 4-methylbenzenesulfonic acid (2.91 mmol) is diluted with lambda/,lambda/-dimethylformamide (40 ml_) and the reaction mixture is heated at reflux for 16 h. The reaction mixture is allowed to cool to rt, neutralized with sodium bicarbonate, diluted with water (400 ml_), and is extracted with ethyl acetate (3 x 100 ml_). The combined organic layers are dried (sodium sulfate) and concentrated. The residue is purified by chromatography (10/1 petroleum ether/ethyl acetate) to provide 5,6,7,8-tetrahydroquinolin-5-one in 7% yield as a colorless oil. |
toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 140℃; for 18h; | To a solution of 10.12 g (0.14 mmol) 3-aminocyclohex-2-en-l-one and 22 mL 1,1,3,3- tetraethoxypropane in 40 mL dry DMF under nitrogen atmosphere was added 0.5 g (cat.) p- toluenesulfonic acid. The reaction mixture was heated at 140 0C for 18 hr. The volatiles were removed under vacuum and the residue distilled under vacuum to give an oil. This material was further purified by column chromatography on silica gel eluting with hexanes/EtOAc (3/1) then EtOAc (100%) afford 1.75 g of the title compound. LC-MS: (MH)+: 148.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 32 4,5-Dihydro-1H(and 2H)pyrazolo[3,4-fquinoline Following the procedure of Ramalingam, K., et al. (Journal of Medicinal Chemistry, Vol. 20, pp. 664-669 (1977)), from 33.5 g (0.228 mol) of 7,8-dihydro-5(6H)-quinolinone (Example 1) is obtained 25.0 g (64%) of the title compound after recrystallization from acetonitrile; mp 206-211 C. |
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