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Structure of 13781-67-4

Chemical Structure| 13781-67-4

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Product Details of [ 13781-67-4 ]

CAS No. :13781-67-4
Formula : C6H8OS
M.W : 128.19
SMILES Code : OCCC1=CSC=C1
MDL No. :MFCD00009766
InChI Key :YYPNNBPPDFTQFX-UHFFFAOYSA-N
Pubchem ID :83731

Safety of [ 13781-67-4 ]

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

Computational Chemistry of [ 13781-67-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 35.25
TPSA ?

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

48.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.63
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

1.22
Log Po/w (WLOGP)?

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

1.28
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.

0.84
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

2.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.53

Water Solubility

Log S (ESOL):?

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

-1.73
Solubility 2.37 mg/ml ; 0.0185 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.84
Solubility 1.87 mg/ml ; 0.0146 mol/l
Class?

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

Very 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

-1.86
Solubility 1.77 mg/ml ; 0.0138 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

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.

-6.22 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

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)

1.85

Application In Synthesis of [ 13781-67-4 ]

* 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 [ 13781-67-4 ]

[ 13781-67-4 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 6964-21-2 ]
  • [ 13781-67-4 ]
YieldReaction ConditionsOperation in experiment
99% Step 2: 2-(thiophen-3-yl)ethanol Tetrahydrofuran (200 mL) was added to LiAlH4 (4.56 g, 0.12 mol) and the mixture was stirred at 0 C. 2-(thiophen-3-yl)acetic acid (14.2 g, 0.1 mol) in THF (100 mL) was added dropwise at this temperature. After the addition, the reaction mixture was stirred at 0 C. for further 2 hours. To the reaction mixture was added EtOAc (200 mL) slowly and then 5 mL of water. The suspension was filtered though ceilite, the filtrate was dried over anhydrous sodium sulfate and concentrated to dryness to afford 2-(thiophen-3-yl)ethanol (12.44 g, yield: 99%). 1H NMR (MeOD, 400 MHz): δ5.92-5.87 (m, 1H), 5.69-5.66 (m, 1H), 5.57 (s, 1H) 2.90 (d, J=14.0 Hz, 1H), 2.38 (d, J=14 Hz, 1H), 1.55-1.42 (m, 2H).
98% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 3h;Schlenk technique; Inert atmosphere; In a flame-dried Schlenk flask, equipped with a magnetic stirring bar, an argon inlet, and a septum, LiAlH4 (5.7 g, 150 mmol, 1.5 equiv) was dissolved in THF (100 mL) at 0 C. A solution of 3-thienylacetic acid (3, 14.2 g, 100 mmol, 1.0 equiv) in THF (50 mL) at 0 C was added dropwise. The mixture was stirred for 3 h at 0 C and then it was carefully quenched with EtOAc and EtOH. Subsequently, 1-2% NaOH (20 mL) was added and the mixture was stirred for 1 h, allowing aluminum hydroxide to precipitate as a granular solid. Finally, the mixture was filtered over Celite. The collected organic layers were dried (MgSO4), and the solvent was evaporated in vacuo to give the pure alcohol 4 (12.5 g, 98%) as a pale yellow oil.
78% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 7h; To a 0 C cooled stirred suspension of lithium aluminiumhydride (8.0 g, 0.21 mol) in THF (100 mL) was added 3-Thiopheneaceticacid 01 (20 g, 0.14 mol) in THF (100 mL) drop wise over1 h. Reaction mixture was warmed to room temperature and stirredfor 6 h. Reaction progress was checked by TLC for completionand then quenched with 10% NaOH solution. The mixture was filteredover Celite, washed with ethylacetate. Aqueous layer wasextracted with ethylacetate and the combined organic layer waswashed with brine. Dried over sodium sulfate and concentratedto yield 2 as a yellow liquid (14.2 g, 78%) 1H NMR (MeOD, 400MHz): d 5.92-5.87 (m, 1H), 5.69-5.66 (m, 1H), 5.57 (s, 1H) 2.90(d, J = 14.0 Hz, 1H), 2.38 (d, J = 14 Hz, 1H), 1.55-1.42 (m, 2H). 13CNMR (DMSO d6, 100 MHz): 145.53, 129.13, 126.54, 121.45,64.46, 38.85; ESI-MS m/z: (Calcd for C6H8OS: 128.03); Found:128.9 [M+H]+.
With lithium aluminium tetrahydride;Inert atmosphere; General procedure: The majority of alcohols were commercially available. Alcohols 9c,26 9i,27 9j28 and 9k29 were prepared by LiAlH4 reduction of the corresponding carboxylic acids and gave spectral data consistent with those in the literature.
3.59 g With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 1.25h; Step 1: 2-(3-Thienyl)ethanol [00367] A solution of thiophene-3-acetic acid (4.982 g, 35.04 mmol) in THF ( 120 mL, 1500 mmol) was cooled to 0 C, and lithium tetrahydroaluminate ( 1 .596 g, 42.05 mmol) was added slowly over 15 min. The reaction was allowed to warm to rt and stirred for 2hrs. The reaction was quenched via addition of water (5 mL) and EtOAc ( 10ml). The mixture was filtered, and the filter cake was washed with 30ml EtOAc. The filtrate was concentrated in vacuo to afford the title compound (3.59 g). NMR (400 MHz, Chloroform-d) δ 7.31 (dd, J = 4.9, 3.0 Hz, 1 H), 7.1 1 - 7.05 (m, 1 H), 7.05 - 6.97 (m, 1 H), 3.87 (t, J = 6.4 Hz, 2H), 2.92 (t, J = 6.4 Hz, 2H), 1.71 (s, 1 H).

  • 2
  • [ 13781-67-4 ]
  • [ 40263-57-8 ]
  • [ 1189815-78-8 ]
YieldReaction ConditionsOperation in experiment
90% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; Example 7; 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine; 13 To a solution containing <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> 12 (1.85 g, 8.37 mmol), 2-(3-thienyl)ethanol (1.20 mL, 10.9 mmol), and triphenylphosphine (2.85 g, 10.9 mmol) in tetrahydrofuran (46.2 mL, 5.70 mmol) was added diisopropyl azodicarboxylate (2.14 mL, 10.9 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and purified by flash chromatography EtOAc/Hex (0-100%) eluted at 30% to give 13 (yield 90%). MS: (ESI+) 332.2
90% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 18h; Step 1: 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine To a solution containing <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (1.85 g, 8.37 mmol), 2-(3-thienyl)ethanol (1.20 mL, 10.9 mmol), and triphenylphosphine (2.85 g, 10.9 mmol) in tetrahydrofuran (46.2 mL, 5.70 mmol) was added diisopropyl azodicarboxylate (2.14 mL, 10.9 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and purified by flash chromatography EtOAc/Hex (0-100%) eluted at 30% to give 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine (yield 90%). MS: (ESI+) 332.2
 

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