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Chemical Structure| 32822-84-7 Chemical Structure| 32822-84-7

Structure of 32822-84-7

Chemical Structure| 32822-84-7

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Product Details of [ 32822-84-7 ]

CAS No. :32822-84-7
Formula : C8H10O3S
M.W : 186.23
SMILES Code : O=C(C1=C(O)C(C)=C(C)S1)OC
MDL No. :MFCD15071706
InChI Key :UKXGHKYPVCZEIW-UHFFFAOYSA-N
Pubchem ID :54691275

Safety of [ 32822-84-7 ]

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

Computational Chemistry of [ 32822-84-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 5
Fraction Csp3 0.38
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.55
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.

2.33
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

2.75
Log Po/w (WLOGP)?

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

1.86
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.

0.97
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

2.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.14

Water Solubility

Log S (ESOL):?

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

-2.9
Solubility 0.233 mg/ml ; 0.00125 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.

-3.98
Solubility 0.0197 mg/ml ; 0.000106 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

-1.94
Solubility 2.12 mg/ml ; 0.0114 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

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.

-5.48 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)

2.67

Application In Synthesis of [ 32822-84-7 ]

* 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 [ 32822-84-7 ]

[ 32822-84-7 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 32822-84-7 ]
  • [ 144677-16-7 ]
  • 2
  • [ 32822-84-7 ]
  • [ 75-26-3 ]
  • [ 133753-53-4 ]
  • 3
  • [ 32822-84-7 ]
  • [ 106-89-8 ]
  • [ 177974-16-2 ]
  • 4
  • [ 32822-84-7 ]
  • [ 3132-64-7 ]
  • [ 177974-16-2 ]
  • 5
  • [ 32822-84-7 ]
  • [ 77-78-1 ]
  • [ 113589-36-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetone; PREPARATION 16 Methyl 4,5-dimethyl-3-methoxythiophene-2-carboxylate To a solution of methyl 3-hydroxy-4,5-dimethylthiophene-2-carboxylate (Preparation 1) (29.7 g, 160 mmol) in anhydrous acetone (500 ml) was added anhydrous potassium carbonate (24.5 g, 178 mmol) and the mixture stirred for 1 hour at room temperature. Dimethyl sulphate (22.4 g, 178 mmol) was added and the mixture stirred under reflux for 2.5 hours. The solvent was evaporated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was washed with brine, dried with sodium sulphate and evaporated to give crude product which was used in the following preparation.
With potassium; In acetone; PREPARATION 2 Methyl 4,5-dimethyl-3-methoxythiophene-2-carboxylate To a solution of methyl 3-hydroxy-4,5-dimethylthiophene-2-carboxylate (Preparation 1) (29.7 g, 160 mmol) in anhydrous acetone (500 ml) was added anhydrous potassium carbonte (24.5 g, 178 mmol) and the mixture stirred for 1 hour at room temperature. Dimethyl sulphate (22.4 g, 178 mmol) was added and the mixture stirred under reflux for 2.5 hours. The solvent was evaporated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was washed with brine, dried with sodium sulphate and evaporated to give crude product which was used in the following preparation.
  • 8
  • [ 32822-84-7 ]
  • [ 83261-28-3 ]
  • 9
  • [ 32822-84-7 ]
  • [ 83261-27-2 ]
  • 10
  • [ 32822-84-7 ]
  • [ 113589-55-2 ]
  • 11
  • [ 32822-84-7 ]
  • [ 113588-92-4 ]
  • 12
  • [ 609-14-3 ]
  • methanolic potassium hydroxide [ No CAS ]
  • [ 2365-48-2 ]
  • [ 32822-84-7 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In methanol; PREPARATION 1 Methyl 4,5-dimethyl-3-hydroxythiophene-2-carboxylate Dry hydrogen chloride gas was bubbled through a mixture of ethyl 2-methyl-3-oxobutanoate (7.6 g, 50 mmol) and methyl 2-mercaptoacetate (11.2 g, 100 mmol) at -10 C. until saturated. The oil was allowed to stand for 3 hours at room temperature, diluted with dichloromethane and washed with brine. After drying with sodium sulphate and evaporation of solvent the oil was dissolved in methanol (10 ml) and added dropwise to methanolic potassium hydroxide (2N; 75 ml), stirring at room temperature for 1 hour. The solution was diluted with iced water (125 ml) and acidified with 3N hydrochloric acid at -3 to 0 C. to pH1. The precipitate was filtered and washed with water (5.5 g, m.p. 50-51 C., methanol).
  • 13
  • [ 609-14-3 ]
  • [ 2365-48-2 ]
  • [ 32822-84-7 ]
YieldReaction ConditionsOperation in experiment
With sodium; EXAMPLE 2 Methyl 3-hydroxy-4,5-dimethyl-2-thiophenecarboxylate Prepared by the method described in Example 1 from ethyl alpha-methyl acetoacetate (29 g, 0.20 moles), methyl thioglycolate (45 g, 0.40 moles) and sodium (10.2 g, 0.44 moles). Recrystallization from methanol gave the product (15.2 g); mp 52-54 C.
With sodium; EXAMPLE 2 Methyl 3-hydroxy-4,5-dimethyl-2-thiophenecarboxylate. Prepared by the method described in Example 1 from ethyl alpha-methyl acetoacetate (29 g, 0.20 moles), methyl thioglycolate (45 g, 0.40 moles) and sodium (10.2 g, 0.44 moles). Recrystallization from methanol gave the product (15.2 g); mp 52-54C.
 

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