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Structure of 52057-98-4

Chemical Structure| 52057-98-4

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Product Details of [ 52057-98-4 ]

CAS No. :52057-98-4
Formula : C12H12N2O
M.W : 200.24
SMILES Code : NC1=CC=C(C2=CC=C(OC)C=C2)N=C1
MDL No. :MFCD05864840
InChI Key :DUYYTOFLIZLBKH-UHFFFAOYSA-N
Pubchem ID :2763993

Safety of [ 52057-98-4 ]

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

Computational Chemistry of [ 52057-98-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 60.57
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

48.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.91
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

1.8
Log Po/w (WLOGP)?

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

2.35
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.

1.14
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

2.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.89

Water Solubility

Log S (ESOL):?

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

-2.68
Solubility 0.423 mg/ml ; 0.00211 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.

-2.43
Solubility 0.744 mg/ml ; 0.00372 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

-4.32
Solubility 0.00969 mg/ml ; 0.0000484 mol/l
Class?

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

Moderately 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

Yes
Log Kp (skin permeation)?

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

-6.24 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

0.0
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

0.0 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)

1.73

Application In Synthesis of [ 52057-98-4 ]

* 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 [ 52057-98-4 ]

[ 52057-98-4 ] Synthesis Path-Downstream   1~8

YieldReaction ConditionsOperation in experiment
With iron; ammonium chloride; In ethanol; water; at 70 - 80℃; for 1.0h; General procedure: Ethanol (20 ml) and water (5 ml) was mixed, added with iron powder, and heated to 70-80C. Ammonium chloride (0.1 g, 2.1 mmol) was added, followed by 2-phenyl-5-nitropyridine (2.0 g, 10.0 mmol) obtained in (i). The reaction was carried out at 70-80C for 1 hour. After the completion of the reaction, the iron powder was filtered while hot through Celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in isopropyl alcohol, crystallized and filtered with addition of water to give the title compound (1.4 g, 81.9%).
With iron; ammonium chloride; In ethanol; water; at 70 - 80℃; for 1.0h; General procedure: Ethanol (20 ml) and water (5 ml) was mixed, added with iron powder, and heated to 70-80C. Ammonium chloride (0.1 g, 2.1 mmol) was added, followed by 2-phenyl-5-nitropyridine (2.0 g, 10.0 mmol) obtained in (i). The reaction was carried out at 70-80C for 1 hour. After the completion of the reaction, the iron powder was filtered while hot through Celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in isopropyl alcohol, crystallized and filtered with addition of water to give the title compound (1.4 g, 81.9%).
  • 2
  • [ 5350-93-6 ]
  • [ 5720-07-0 ]
  • [ 52057-98-4 ]
  • 3
  • [ 13534-97-9 ]
  • [ 5720-07-0 ]
  • [ 52057-98-4 ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux; General procedure: To 0.329 g (1.5 mmol) 4-iodoaniline, 1.8 mmol ArB(OH)2, 0.318 g (3 mmol) Na2CO3 and 75 mg (0.075 mmol) PdCl2(PPh3)2, 15 mL of a blended solution of dioxane and water (v/v = 3/1) was added under N2 atmosphere. Then the reaction was heated to reflux and monitored by TLC. Upon cooling, the reaction mixture was dilute with sat. NH4Cl solution, then extracted with EA (3×20 mL), and the organic layer was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography to afford different 4-aminobiphenyl derivatives. According to the reductive amination procedure, the 4-aminobiphenyl derivative was further treated with salicylaldehyde and to afford the corresponding compound 5&6.
  • 4
  • [ 52057-98-4 ]
  • [ 90-02-8 ]
  • 2-(((6-(4-methoxyphenyl)pyridin-3-yl)amino)methyl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Under an atmosphere of N2, 0.175 g (1 mmol) compd. 2 was dissolved in methanol, 0.11 mL (1.05 mmol) salicylaldehyde was added and stirred overnight at room temperature. When compd. 2 disappeared, NaBH4 (61 mg, 1.6 mmol) was added. After stirring for 10 min, the reaction was quenched by sat. NH4Cl solution, then extracted with CH2Cl2 (3×20 mL), and the organic layer was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE:EtOAc = 15:1) to afford 0.230 g (82%) E6 as white solid.
  • 5
  • [ 52057-98-4 ]
  • [ 211733-67-4 ]
  • N<SUP>2</SUP>-(4-aminocyclohexyl)-9-cyclopentyl-N<SUP>6</SUP>-(6-(4-methoxyphenyl)pyridin-3-yl)-9H-purine-2,6-diamine [ No CAS ]
  • 6
  • [ 52057-98-4 ]
  • [ 211733-67-4 ]
  • (2-chloro-9-cyclopentyl-9H-purin-6-yl)-[6-(4-methoxyphenyl)pyridin-3-yl]amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With N-ethyl-N,N-diisopropylamine; In propan-1-ol; at 100℃;Sealed tube; To a suspension of 9-substituted-2,6-dichloro-9H-purine (8)(2.00 mmol) in a mixture of n-propanol (10 mL) and N,N-diisopropyl-N-ethylamine (6.00 mmol), appropriate amine (2.05 mmol)was added. The suspension was heated while stirring in a sealedtube under an argon atmosphere at 100 C for 2-6 h. The reactionwas checked by TLC using mobile phase toluene-ethylacetate (1:1,v/v). After the completion of the reaction, the reaction mixture wascooled to room temperature and evaporated under reduced pressure.The residue was partitioned between water (50 mL) and dichloromethane (50 mL), and the water phase was extracted twoadditional times with the same volume of dichloromethane. Thecombined organic phases were washed with water and brine andevaporated under reduced pressure. The crude product was crystallizedfrom petroleum ether/ethylacetate (3:1).
  • 7
  • [ 131941-25-8 ]
  • [ 52057-98-4 ]
YieldReaction ConditionsOperation in experiment
With 5%-palladium/activated carbon; hydrogen; In methanol; under 760.051 Torr; General procedure: The crude nitroderivative (5) from the previous step(0.75 mmol) was hydrogenated under atmospheric pressure inmethanol (50 mL) with 5% wt. palladium on charcoal (50 mg). Afterthe consumption of hydrogen, the reaction mixture was filteredthrough Celite, washed with methanol and evaporated underreduced pressure. The crude product was dissolved in 2M hydrochloricacid (50 mL) and extracted with dichloromethane (25 mL).The water phase was neutralized with 5% sodium hydrogen carbonate,and the precipitate was filtered off and washed with water.The crude product was dried in a vacuum desiccator and finallypurified by flash column chromatography using mobile phasechloroform/methanol (4:1, v/v).
  • 8
  • [ 4487-59-6 ]
  • [ 52057-98-4 ]
 

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