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Chemical Structure| 205-95-8 Chemical Structure| 205-95-8

Structure of 205-95-8

Chemical Structure| 205-95-8

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Product Details of [ 205-95-8 ]

CAS No. :205-95-8
Formula : C18H11N
M.W : 241.29
SMILES Code : N12C3=C(C4=C1C(C5=C2C=CC=C5)=CC=C4)C=CC=C3
MDL No. :MFCD01851757
InChI Key :SZLNOBJKCVERBJ-UHFFFAOYSA-N
Pubchem ID :15352087

Safety of [ 205-95-8 ]

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

Computational Chemistry of [ 205-95-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 19
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 81.1
TPSA ?

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

4.41 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.8
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

4.7
Log Po/w (WLOGP)?

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

4.84
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.

4.32
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

4.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.18

Water Solubility

Log S (ESOL):?

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

-5.04
Solubility 0.00222 mg/ml ; 0.00000918 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.52
Solubility 0.00727 mg/ml ; 0.0000301 mol/l
Class?

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

Moderately 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

-6.65
Solubility 0.000054 mg/ml ; 0.000000224 mol/l
Class?

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

Poorly 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

Yes
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

Yes
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.

-4.43 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

1.0
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

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<2.0
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)

1.29

Application In Synthesis of [ 205-95-8 ]

* 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 [ 205-95-8 ]

[ 205-95-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 902518-11-0 ]
  • [ 205-95-8 ]
YieldReaction ConditionsOperation in experiment
95% With palladium diacetate; tricyclohexylphosphine; In N,N-dimethyl acetamide;Reflux; Compound E (9 g, 28 mmol),Pd (OAc) 2 (1.9 g, 0.84 mmol),PCy3 (0.47 g, 1.68 mmol) was added to 100 mL of DMAc and the mixture was refluxed and stirred. After completion of the reaction, water was added, and the mixture was extracted with toluene (25 mL * 3 times)The obtained organic layer was dried over MgSO4, distilled under reduced pressure, and purified through short silica column chromatography (EtOAc: Hexane) to obtain compound J (6.5 g, 95%).
89.5% With N-benzyl-N,N,N-triethylammonium chloride; palladium diacetate; potassium carbonate; triphenylphosphine; In N,N-dimethyl-formamide; at 150℃; for 3h;Inert atmosphere; The preparation method of the compound of formula M2 is as follows:2.87 g (8.0 mmol) of M1, 0.2 g (0.8 mmol) of benzyltriethylammonium chloride, and 5.5 g (40.0 mmol) of potassium carbonate were sequentially added to a 250 mL two-necked flask.Triphenylphosphine, 0.26 g (1.2 mmol) palladium acetate,100 mL of N,N-dimethylformamide,The reaction system is degassed and then protected with nitrogen.The mixture was heated to 150 C with stirring for 3 hours. After the reaction is completed, the system is cooled to room temperature and poured into water.Filter under reduced pressure and wash the filter residue with plenty of water.The filter residue was used in dichloromethane: petroleum ether = 1:20The (volume ratio) eluent was separated and purified on a silica gel column to obtain 1.7 g of M2 in a yield of 89.5%.
83% With Et3NBnCl; palladium diacetate; potassium carbonate; triphenylphosphine; In N,N-dimethyl acetamide; for 6h;Inert atmosphere; Reflux; General procedure: A mixture of 3aa (200 mg, 0.62 mmol), anhydrous K2CO3 (428 mg, 3.1 mmol), PPh3 (60 mg, 0.22 mmol), BnEt3NCl (133 mg, 0.62 mmol) and Pd(OAc)2 (21 mg, 0.09 mmol) in DMA (50 mL) in a 100 mL three-necked flask was refluxed for 6 h under nitrogen, then it was cooled to room temperature and poured into ice-water (200 mL). Subsequent extraction with CH2Cl2 was made and the combined organic phase was washed with water and dried over MgSO4. After workup, the crude product was purified with PE (Rf = 0.41) to afford 4aa as a white solid (124.0 mg, 83 %); m. p.: 126 - 128 C; 1H NMR (CDCl3, 500 MHz) delta: 8.12 (d, J = 7.70 Hz, 2H), 8.02 (d, J = 7.4 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.55 (m, 3H), 7.34 (t, J = 7.53 Hz, 2H); 13C NMR (CDCl3, 125 MHz) delta: 143.75, 138.70, 130.03, 126.68, 123.14, 122.81, 121.67, 119.38, 118.45, 112.14; MS (EI): m/z=241[M+].
47% With palladium diacetate; potassium carbonate; ammonium bromide; triphenylphosphine; In N,N-dimethyl acetamide; at 150℃; for 20h; To a 3000-mL four-necked round-bottomed flask was added 22 g (0.069 mol) of the compound 11-1 prepared in Example 1-1, 1.6 g of palladium acetate (II), 3.6 g of triphenylphosphine, 43 g of potassium carbonate, 11 g of ammonium bromide and 2200 mL of dimethyl acetamide. The reaction solution was stirred at 150 C for 20 hours, and then dimethylacetamide was concentrated under reduced pressure. The concentrate was diluted with dichloromethane and extracted with dichloromethane and distilled water. The extract was dried and concentrated under reduced pressure. The obtained crude product was subjected to column separation to obtain 7.8 g (yield 47%) of Compound 11-2.

 

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