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Chemical Structure| 898566-17-1 Chemical Structure| 898566-17-1

Structure of 898566-17-1

Chemical Structure| 898566-17-1

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Product Details of [ 898566-17-1 ]

CAS No. :898566-17-1
Formula : C18H14FIS
M.W : 408.27
SMILES Code : CC1=C(CC2=CC=C(S2)C2=CC=C(F)C=C2)C=C(I)C=C1
MDL No. :MFCD12405593
InChI Key :MGXZKAYHSITHMW-UHFFFAOYSA-N
Pubchem ID :45789954

Safety of [ 898566-17-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 898566-17-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 17
Fraction Csp3 0.11
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 96.85
TPSA ?

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

28.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.79
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

6.34
Log Po/w (WLOGP)?

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

6.48
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.

5.92
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

7.97
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

6.1

Water Solubility

Log S (ESOL):?

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

-6.77
Solubility 0.0000699 mg/ml ; 0.000000171 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

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

-6.72
Solubility 0.0000772 mg/ml ; 0.000000189 mol/l
Class?

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

Poorly 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

-8.64
Solubility 0.000000944 mg/ml ; 0.0000000023 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

No
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

Yes
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

Yes
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.

-4.29 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

1.0
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

2.0
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<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)

3.06

Application In Synthesis of [ 898566-17-1 ]

* 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 [ 898566-17-1 ]

[ 898566-17-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1030825-20-7 ]
  • [ 898566-17-1 ]
YieldReaction ConditionsOperation in experiment
With sodium iodide; N,N`-dimethylethylenediamine;copper(l) iodide; In diethylene glycol dimethyl ether; toluene; at 110℃; Example 3; 2-(4-Fluoro-phenyl)-5-(5-iodo-2-methyl-benzyl)-thiopheneA 1.0 L four-necked reaction flask was charged with the compound prepared as in Example 2 above (100 g, 276.80 mmoles), sodium Iodide (82 g, 553.59 mmoles) and Copper(l) Iodide (2.6 g, 13.84 mmoles). The resulting mixture was evacuated and purged with argon, then treated with toluene (261 ml_), diglyme (56 ml_) and N,N'-dimethyl-ethane-1 ,2-diamine (2.7 ml_, 27.68 mmoles) and the resulting mixture warmed to 11 O0C overnight. Upon consumption of starting material, the resulting mixture was cooled to room temperature, then filtered through Celite.(R)., washed with EtOAc, and extracted with NH4OH. The organic phase was dried (Na2SO4), filtered and concentrated to yield a solid. The solids were filtered and recrystallized from heptane to yield the title compound as an off white solid (m.p. 1070C). (See also, Klaper, A., Buchwald, S. L., "Copper-Catalyzed HalogenExchange in Aryl Halides: An Aromatic Finkelstein Reaction", J. Am. Chem. Soc, 2002, 124, 14844-14814)
With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine; In diethylene glycol dimethyl ether; toluene; at 20℃;Inert atmosphere; Reflux; Example 15; 2-(4-fluorophenyl)-5(5-iodo-2-methylbenzyl)thiophene 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (100 g); (see Nomura S., et al., PCT Publication, WO 2005/012326 A1, published Feb. 10, 2005) was dissolved in toluene (300 mL) at room temperature under N2 atmosphere. Sodium iodide (83 g), copper (I) iodide (2.64 g), N,N'-dimethyl ethylenediamine (2.94 mL) and diglyme (50 mL) was added to the mixture at room temperature. The reaction mixture was heated to reflux temperature and stirred for 36 hours. Ethyl acetate (300 mL) was added to the mixture at 40° C. and the mixture was filtered using activated carbon pre-coated filter. The filtrate was washed twice with 5percent aqueous NH3 solution (100 mL). The organic layer was washed with water (100 mL) and then evaporated. The resulting residue was suspended in methanol (426 mL) at reflux temperature for 75 minutes. The resulting slurry was cooled to 25° C. and stirred for 1 hour. The precipitate was filtered and washed with methanol, then dried at 50° C. in vacuo to give 2-(5-iodo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (94.9 g) as white crystals.m/z (APCI), 409(M++H); mp 109-110° C.; 1H NMR (400 MHz, CDCl3); delta 7.54 (d, 4JHH=1.8 Hz, 1H), 7.45-7.42 (m, 3H), 7.07-6.99 (m, 3H), 6.92 (d, 3JHH=6.0 Hz, 1H), 6.66 (d, 3JHH=3.6 Hz, 1H), 4.05 (s, 2H), 2.26 (s, 3H).
94.9 g With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine; In diethylene glycol dimethyl ether; toluene; for 36h;Inert atmosphere; Reflux; 10098] 2-(5-Bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (100 g; see WO 2005/012326 pamphlet) was dissolved in toluene (300 mL) at room temperature under N2 atmosphere. Sodium iodide (83 g), copper (I) iodide (2.64 g), N,N?-dimethyl ethylenediamine (2.94 mL) and diglyme (50 mL) was added to the mixture at room temperature. The reaction mixture was heated to reflux temperature and stirred for 36 hours. Ethyl acetate (300 mL) was added to the mixture at 40° C. and the mixture was filtered using activated carbon pre-coated filtet The filtrate was washed and then evaporated. The resulting residue was suspended in methanol (426 mL) at reflux temperature for 75 minutes. The resulting slurry was cooled to 25° C. and stirred for 1 hout The precipitate was filtered and washed with methanol, then dried at 50° C. in vacuo to give 2-(5-iodo-2-methylbenzyl)-5-(4-fluorophenyl) thiophene (94.9 g) as white crystals. mlz (APCI), 409 (M+ H);mp 109-110° C.
 

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