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Chemical Structure| 18978-78-4 Chemical Structure| 18978-78-4

Structure of 18978-78-4

Chemical Structure| 18978-78-4

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Product Details of [ 18978-78-4 ]

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

Safety of [ 18978-78-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 18978-78-4 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

38.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.71
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.0
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.13
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.49
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.21
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.91

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.7
Solubility 0.317 mg/ml ; 0.00201 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.44
Solubility 0.57 mg/ml ; 0.0036 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.72
Solubility 0.0304 mg/ml ; 0.000192 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.85 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.18

Application In Synthesis of [ 18978-78-4 ]

* 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.

  • Downstream synthetic route of [ 18978-78-4 ]

[ 18978-78-4 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 18978-78-4 ]
  • [ 37091-73-9 ]
  • [ 1392814-28-6 ]
  • 2
  • [ 18978-78-4 ]
  • [ 42926-52-3 ]
  • 2-ethoxy-N-(2-methylquinolin-8-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation 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]+.
  • 3
  • [ 18978-78-4 ]
  • [ 7697-25-8 ]
  • 2-chloro-4-methyl-N-(2-methylquinolin-8-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation 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]+.
  • 4
  • [ 18978-78-4 ]
  • [ 15893-42-2 ]
  • 3-(4-methoxyphenyl)-N-(2-methylquinolin-8-yl)propanamide [ No CAS ]
YieldReaction ConditionsOperation 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]+.
  • 5
  • [ 18978-78-4 ]
  • [ 652-12-0 ]
  • C26H6F8N2O4 [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 6
  • [ 18978-78-4 ]
  • [ 652-12-0 ]
  • [ 117-08-8 ]
  • C26H6Cl4F4N2O4 [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 7
  • [ 18978-78-4 ]
  • [ 51997-51-4 ]
  • 1-((9H-carbazol-4-yl)oxy)-3-((2-methylquinolin-8-yl)amino)propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation 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.
 

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Technical Information

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