Structure of 18978-78-4
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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. : | 18978-78-4 |
Formula : | C10H10N2 |
M.W : | 158.20 |
SMILES Code : | C2=CC1=CC=CC(=C1N=C2C)N |
MDL No. : | MFCD00023998 |
InChI Key : | JHIAOWGCGNMQKA-UHFFFAOYSA-N |
Pubchem ID : | 140457 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.21 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.7 |
Solubility | 0.317 mg/ml ; 0.00201 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.44 |
Solubility | 0.57 mg/ml ; 0.0036 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.72 |
Solubility | 0.0304 mg/ml ; 0.000192 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) |
Yes |
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 |
-5.85 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 |
1.0 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) |
1.18 |
* 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 |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 2.5h; | [00405] 2-Ethoxybenzoyl chloride (185 mg, 1.0 mmol) was dissolved in dichloromethane (2 mL) and cooled to 0 C. This solution was added dropwise to a cooled (0 C) solution of 8- aminoquinaldine (158 mg, 1.0 mmol) and N,N-diisopropylethylamine (260 jiL, 1.5 mmol) in dichloromethane (5 mL). After addition was complete, the mixture was allowed to warm to room temperature and stirred for 2.5 hrs. The mixture was diluted with water and extracted with 2 volumes of dichloromethane. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford compound A10. ESI-MS: m/z 307 [M+H]. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 2.5h; | 2-Ethoxybenzoyl chloride (185 mg, 1.0 mmol) was dissolved in dichloromethane (2 mL) and cooled to 0 C. This solution was added dropwise to a cooled (0 C.) solution of 8-aminoquinaldine (158 mg, 1.0 mmol) and N,N-diisopropylethylamine (260 muL, 1.5 mmol) in dichloromethane (5 mL). After addition was complete, the mixture was allowed to warm to room temperature and stirred for 2.5 hrs. The mixture was diluted with water and extracted with 2 volumes of dichloromethane. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford compound A10. ESI-MS: m/z 307 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00412] <strong>[7697-25-8]2-Chloro-4-methylbenzoic acid</strong> (171 mg, 1.0 mmol) and N-(3-dimethylaminopropyl)- N?-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (260 jiL, 1.5 mmol) was added and the solution was stirred for 10 minutes. To this solution was added 8-aminoquinaldine (158 mg, 1.0 mmol) and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a wateracetonitrile gradient to afford compound A17. ESI-MS: m/z 311 [M+H]. | ||
<strong>[7697-25-8]2-Chloro-4-methylbenzoic acid</strong> (171 mg, 1.0 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (260 muL, 1.5 mmol) was added and the solution was stirred for 10 minutes. To this solution was added 8-aminoquinaldine (158 mg, 1.0 mmol) and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford compound A17. ESI-MS: m/z 311 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 2.5h; | [00418] 3-(4-Methoxyphenyl)propionyl chloride (199 mg, 1.0 mmol) was dissolved in dichloromethane (2 mL) and cooled to 0 C. This solution was added dropwise to a cooled (0C) solution of 8-aminoquinaldine (158 mg, 1.0 mmol) and N,N-diisopropylethylamine (260 jiL,1.5 mmol) in dichloromethane (5 mL). After addition was complete, the mixture was allowed to warm to room temperature and stirred for 2.5 hrs. The mixture was diluted with water and extracted with 2 volumes of dichloromethane. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford compound A23. ESI-MS: m/z 321 [M+H]. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 2.5h; | 3-(4-Methoxyphenyl)propionyl chloride (199 mg, 1.0 mmol) was dissolved in dichloromethane (2 mL) and cooled to 0 C. This solution was added dropwise to a cooled (0 C.) solution of 8-aminoquinaldine (158 mg, 1.0 mmol) and N,N-diisopropylethylamine (260 μL, 1.5 mmol) in dichloromethane (5 mL). After addition was complete, the mixture was allowed to warm to room temperature and stirred for 2.5 hrs. The mixture was diluted with water and extracted with 2 volumes of dichloromethane. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford compound A23. ESI-MS: m/z 321 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
As shown in Reaction Scheme 2 above,(B) Compound 1.58 g (0.01 mol) of 8-aminoquinaldine (c)Tetra fluoro phthalic anhydride (0.01 mol) and 40 g of trichlorobenzene were added and refluxed for 4 hours at 220 C. After the reaction was completed, tetrafluorophthalic anhydride (0.01 mol) and 0.45 g (0.003 mol) ZnCl 2 were added again, the reaction is refluxed for 5 hours. When the reaction is completed, the reaction mixture is cooled to room temperature, and the reaction solution is slowly added to 1 L of n-hexane to precipitate.The resulting solid was filtered under reduced pressure, washed with 1% aqueous sodium hydroxide solution dry in a vacuum oven for one day.The resulting dye was dissolved in chloroform, filtered under reduced pressure, the filtrate is evaporated to remove the solvent.And purified by EA: HEXANE = 1.5: 1 column chromatography to obtain the compound represented by formula (2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | To 100 parts of methyl benzoate,40 parts of 8-aminoquinaldine,128 parts of tetrafluorophthalic anhydride,93 parts of benzoic acid was added,The mixture was heated to 180 C. and stirred for 6 hours while distilling off water. After cooling to room temperature,The reaction mixture was poured into 1,200 parts of methanol and stirred at room temperature for 1 hour.The precipitated crystals were filtered off, washed with methanol again,And dried under reduced pressure. Subsequently, 900 parts of water,150 parts of potassium hydroxide was added and the mixture was heated to 90 C. and stirred for 16 hours.After cooling to room temperature, 200 parts of 36% hydrochloric acid was added dropwise. The precipitated crystals were filtered off,Further, it was washed with methanol and dried under reduced pressure. Subsequently, the above-To 250 parts of methyl benzoate, 87 parts of tetrachlorophthalic anhydride was further added, heated to 180 C. and stirred for 5 hours while distilling off water. After cooling to room temperature,The reaction mixture was poured into 1,400 parts of methanol and stirred at room temperature for 1 hour.The precipitated crystals were separated by filtration, further washed with methanol, dried under reduced pressure,151 parts (yield: 95%) of the quinophthalone compound (B-1) was obtained.As a result of mass spectrometry by TOF-MS,It was identified as a quinophthalone compound (B-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In isopropyl alcohol; for 5h;Inert atmosphere; Reflux; | General procedure: Corresponding 2-(aryloxymethyl)oxiranes (5 mmol, 1 equiv) and amines (7.5 mmol, 1.5 equiv) were dissolved in 30 mL i-PrOH. The reaction was purged with argon 3 times and stirred at reflux for 5 h, andthen the mixture was cooled to room temperature and added AcOEt.After washing with brine 3 times, the organic layer was dried overanhydrous Na2SO4, filtered, and evaporated in vacuo. Purification ofthe crude residue by column chromatography on silica gel yielded target compounds. |