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Chemical Structure| 5335-40-0 Chemical Structure| 5335-40-0

Structure of 5335-40-0

Chemical Structure| 5335-40-0

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Product Details of [ 5335-40-0 ]

CAS No. :5335-40-0
Formula : C7H7ClO4S2
M.W : 254.71
SMILES Code : O=S(C1=CC=CC(S(=O)(C)=O)=C1)(Cl)=O
MDL No. :MFCD04037968
InChI Key :CQEFJGDLGWJIRV-UHFFFAOYSA-N
Pubchem ID :220330

Safety of [ 5335-40-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 5335-40-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 52.62
TPSA ?

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

85.04 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.32
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

1.58
Log Po/w (WLOGP)?

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

3.18
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.

1.03
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

0.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.56

Water Solubility

Log S (ESOL):?

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

-2.6
Solubility 0.64 mg/ml ; 0.00251 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.

-2.98
Solubility 0.269 mg/ml ; 0.00106 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

-3.25
Solubility 0.142 mg/ml ; 0.000556 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

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

No
Log Kp (skin permeation)?

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

-6.73 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<0.0
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)

2.35

Application In Synthesis of [ 5335-40-0 ]

* 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 [ 5335-40-0 ]

[ 5335-40-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 35216-39-8 ]
  • [ 5335-40-0 ]
YieldReaction ConditionsOperation in experiment
3-Methanesulfonyl-benzenesulfonyl chloride was prepared according to a previously described procedure (Tetrahedron 59 (2003) 1317-1325). 3-Methanesulfonyl- phenylamine (1 gm, 4.8 mmol) was dissolved in CH3CN (40 mL). The solution was cooled in an ice bath (0 - 5 0C) and 4 mL of acetic acid and 2 mL of concentrated HCl were added. To the mixture was added NaNO2 (397 mg, 5.76 mmol, in 3 mL water) over 10 min at 5 0C. After stirring 20 min, SO2 gas was bubbled in over 30 min (~ 200 drops) keeping the reaction mixture < 7 0C. A solution of CuCl2 (840 mg, 6.24 mmol) in water (2.5 mL) was added and the mixture was allowed to warm and stir for 16 h at RT. The mixture was concentrated in vacuo and the remaining mixture was diluted with I N HCl and extracted with EtOAc (3 x 100 mL). The combined organic layer was washed with brine, dried (MgSO4), and evaporated in vacuo to provide 1.2 gm of 3- methanesulfonyl-benzenesulfonyl chloride as a pale yellow solid. 1H-NMR (CDCl3): delta 8.62 (t, IH, J = 1.6 Hz), 8.33-8.36 (m, 2H), 7.92 (t, IH, J = 8.0 Hz), 7.28 (s, IH), and 3.18 (s, 3H).
Into a 100-mL round-bottom flask, was placed a solution of <strong>[35216-39-8]3-(methylsulfonyl)benzenamine</strong>(200 mg, 1.17 mmol) in HC1 (6 M, 5 mL). This was followed by the addition of a solution ofNaNO2 (97 mg, 1.41 mmol) in water (0.5 mL) dropwise with stirring at 0C. The resultingsolution was stirred for 20 mm at 0C. The above mixture was added to a saturated solution of SO2 in AcOH (5 mL) dropwise with stirring at 0C. Then to the above was added CuC12 (157 mg, 1.17 mmol). The resulting solution was stirred for 1 h at RT and then was quenched by the addition of 10 mL of water. The resulting solution was extracted with 3x10 mL of DCM and theorganic layers combined and dried over anhydrous Na2504, then concentrated under vacuum.This resulted in 250 mg (84%) of the title compound as a light yellow solid. The crude productwas used in the next step.
  • 2
  • [ 881674-56-2 ]
  • [ 5335-40-0 ]
  • [ 881677-02-7 ]
YieldReaction ConditionsOperation in experiment
56% Reference Example 240 5-(2-Fluorophenyl)-1-[3-(methylsulfonyl)phenyl]sulfonyl}-1H-pyrrole-3-carbaldehyde To a solution (48 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (475 mg) in tetrahydrofuran was added sodium hydride (60% in oil, 302 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.66 g) was added dropwise and the mixture was stirred for 30 min, [3-(methylsulfonyl)benzene]sulfonyl chloride (1.28 g) was added, and the mixture was further stirred for 15 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3?2:3), and crystallized from diisopropyl ether· ethyl acetate mixed solvent (4:1) to give the title compound as colorless crystals (yield 576 mg, 56%). 1H-NMR(CDCl3) delta:3.03(3H,s), 6.69(1H,d,J=1.8Hz), 6.97-7.02(1H,m), 7.19-7.22(2H,m), 7.43-7.50(1H,m), 7.63-7.75(2H,m), 7.99-8.00(1H,m), 8.14(1H,d,J=1.8Hz), 8.16-8.19(1H,m), 9.91(1H,s).
In tetrahydrofuran; Reference Example 240 5-(2-Fluorophenyl)-1-[3-(methylsulfonyl)phenyl]sulfonyl}-1H-pyrrole-3-carbaldehyde To a solution (48 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (475 mg) in tetrahydrofuran was added sodium hydride (60% in oil, 302 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.66 g) was added dropwise and the mixture was stirred for 30 min, [3-(methylsulfonyl)benzene]sulfonyl chloride (1.28 g) was added, and the mixture was further stirred for 15 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3?2:3), and crystallized from diisopropyl ether-ethyl acetate mixed solvent (4:1) to give the title compound as colorless crystals (yield 576 mg, 56%). 1H-NMR(CDCl3) delta:3.03(3H, s), 6.69(1H, d, J=1.8Hz), 6.97-7.02(1H, m), 7.19-7.22(2H, m), 7.43-7.50(1H, m), 7.63-7.75(2H,m),7.99-8.00(1H,m),8.14(1H,d,J=1.8Hz),8.16-8.19(1H,m),9.91(1H,s).
 

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