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Structure of 5118-06-9

Chemical Structure| 5118-06-9

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Product Details of [ 5118-06-9 ]

CAS No. :5118-06-9
Formula : C6H6O3S
M.W : 158.18
SMILES Code : O=C(C1=C(O)C=CS1)OC
MDL No. :MFCD00055642
InChI Key :SEMVRXMFCHXUMD-UHFFFAOYSA-N
Pubchem ID :581127

Safety of [ 5118-06-9 ]

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

Computational Chemistry of [ 5118-06-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.17
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 37.62
TPSA ?

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

74.77 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.51
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

1.98
Log Po/w (WLOGP)?

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

1.24
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.

0.29
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

1.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.38

Water Solubility

Log S (ESOL):?

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

-2.31
Solubility 0.782 mg/ml ; 0.00494 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.

-3.18
Solubility 0.105 mg/ml ; 0.000667 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

-1.16
Solubility 11.1 mg/ml ; 0.07 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

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

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

No
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.

-5.86 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.

1.0 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)

2.21

Application In Synthesis of [ 5118-06-9 ]

* 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 [ 5118-06-9 ]

[ 5118-06-9 ] Synthesis Path-Downstream   1~3

YieldReaction ConditionsOperation in experiment
Example 1 Synthesis of Representative Thiophene-Containing Monomers Methyl 3-aminothiophene-2-carboxylate was Boc-protected and the resulting ester was saponified to yield 3-[(tert-butoxy)carbonylamino]-2-thiophene-carboxylic acid (11). Methyl 3-hydroxythiophene-2-carboxylate (12) was prepared by cyclization of methylthioglycolate and methyl-2-chloroacrylate in methanolic sodium methoxide (Huddleston et al., Synth. Commun. 1979, 9, 731).
  • 3
  • [ 5118-06-9 ]
  • [ 79756-81-3 ]
  • methyl 3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% Compound 44 (2.10g, 13.29mmol), compound 45 (2.90g, 15.26mmol) and triphenyl phosphine (4.66g, 17.79mmol) was added to DCM (50mL),Stir for 15 min in an ice bath to reduce the solution to 0 C and continue stirring for 20 min.Diisopropyl azodicarboxylate (3.60 g, 17.82 mmol) was added and stirred at room temperature for 5 hours.The reaction solution was spun and separated by silica gel column chromatography using a petroleum ether and ethyl acetate system (PE:EA=150:1 to 60:1).A pale yellow solid 46 (4.03 g, 92%).
92% With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 5h; To a solution of 6 (2.10 g, 13.29 mmol) in DCM (50 mL), commercial compound 7a (2.90 g, 15.26 mmol) and triphenylphosphine (4.66 g,17.79 mmol) was added. After stirring at 0 C for 20 min, diisopropyl azodicarboxylate (3.60 g, 17.82 mmol) was added and stirred at room temperature for 5 h. The reaction solution concentrated under vacuum and the residue was purified by flash chromatography, eluting with a gradient of 1%-5% EA in PE, to give 8a(4.03 g, 92%)as a light yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 7.91 (d, J = 7.8 Hz, 1H), 7.61(d, J = 7.9 Hz, 1H), 7.55 (t, J = 7.3 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.23(dd, J = 5.4, 2.0 Hz, 1H), 6.68 (dd, J = 5.6, 1.6 Hz, 1H), 5.78 (q, J = 6.3Hz, 1H), 3.87 (s, 3H), 1.71 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz,Chloroform-d) δ 161.00, 158.75, 142.16-140.00 (m), 131.81, 129.40,126.54 (d, J = 35.8 Hz), 125.66 (d, J = 30.4 Hz), 125.06 (d, J = 30.4Hz), 124.49 (q, J = 5.8 Hz), 123.36 (d, J = 273.8 Hz), 116.99, 110.13,74.45, 50.51, 23.62. MS (ESI) m/z calcd. for C15H13F3O3S (M+H)+331.05.
63.7% With triphenylphosphine; diethylazodicarboxylate; In dichloromethane; at 20℃; for 12h;Cooling with ice; Methyl 3-hydroxythiophene-2-carboxylate (5 g, 26.8 mmol) and l-(2- (trifluoromethyl)phenyl)ethan-l-ol (5.61 g, 29.5 mmol) were dissolved in DCM (80 mL) and cooled in an ice bath. Following, triphenylphosphine (10.18 g, 38.9 mmol) was added and DEAD (6.97 g, 38.9 mmol) was added dropwise. After the addition, the reaction was removed from the ice bath and stirred at room temperature for 12 hours. The crude reaction was condensed and adsorbed onto silica and purified via flash chromatography using Hexanes/EtOAC. The title compound was isolated as white solid/crystals methyl 3- (l-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylate (6.12 g, 63.7%).
 

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