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Chemical Structure| 5239-82-7 Chemical Structure| 5239-82-7

Structure of 5239-82-7

Chemical Structure| 5239-82-7

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Product Details of [ 5239-82-7 ]

CAS No. :5239-82-7
Formula : C5H8O2
M.W : 100.12
SMILES Code : O=C(O)CC1CC1
MDL No. :MFCD00041544
InChI Key :KVVDRQDTODKIJD-UHFFFAOYSA-N
Pubchem ID :138440

Safety of [ 5239-82-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H315-H318-H335
Precautionary Statements:P261-P280-P305+P351+P338
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 5239-82-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 25.81
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.09
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

0.84
Log Po/w (WLOGP)?

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

0.81
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.

0.5
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

0.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.8

Water Solubility

Log S (ESOL):?

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

-0.86
Solubility 13.9 mg/ml ; 0.139 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.

-1.21
Solubility 6.23 mg/ml ; 0.0622 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

-0.18
Solubility 66.3 mg/ml ; 0.662 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.

-6.31 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.

0.56

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)

1.0

Application In Synthesis of [ 5239-82-7 ]

* 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 [ 5239-82-7 ]

[ 5239-82-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 64-17-5 ]
  • [ 5239-82-7 ]
  • [ 1200828-74-5 ]
YieldReaction ConditionsOperation in experiment
70% Step 1. ethyl bromo(cyclopropyl)acetate Thionyl chloride (0.46 mL, 6.3 mmol) was added dropwise to a solution of cyclopropylacetic acid (0.5 g, 5 mmol) (Oakwood cat003710) in 1,2-dichloroethane (5.2 mL) at room temperature. The reaction was heated to reflux for 2 h then allowed to cool to room temperature, at which time N-bromosuccinimide (1.12 g, 6.27 mmol) and hydrogen bromide (2 mu, 0.04 mmol) (48% aqueous solution) were added successively. The resulting mixture was heated to reflux for 2 days. The reaction mixture was then cooled to room temperature, ethanol (4 mL) was added, and the reaction was stirred at room temperature for an additional 2 h. The reaction mixture was then concentrated to afford the crude product. The crude product was dissolved in carbon tetrachloride and was passed through a short column of silica gel and concentrated to afford ethyl bromo(cyclopropyl)acetate (0.70 g, 70%) as an oil.
Racemic ethyl 2-bromo-2-cyclopropylacetate The above compound was prepared by adding a solution of 2-cyclopropylacetic acid (24.7 g, 247 mmol) in anhydrous DCE (250 mL) to thionyl chloride (22 mL, 302 mmol) dropwise over 5 minutes at 25 C. After refluxing for 2 hours, the reaction was cooled to room temperature, and N-bromosuccinimde (53.6 g, 301 mmol) and hydrogen bromide (48% aqueous solution; 0.195 mL, 1.727 mmol) were added successively at 25 C. The mixture was refluxed for 3 days, then cooled to room temperature. Absolute EtOH (200 mL) was added and the resulting dark brown solution was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the residue was suspended in carbon tetrachloride (300 mL) and filtered through a glass filter. The filtrate was concentrated under the reduced pressure. The crude product was purified by flash chromatography (silica-gel, 330 g x 2, 5 % ethyl acetate in hexanes) to provide ethyl 2-bromo-2-cyclopropylacetate. .H NMR (400 MHz, CDCk) delta ppm 4.24 (m, 2 H), 3.58 (d, J=12.0 Hz, 1H), 1.58 (m, 1H), 0.90-0.80 (m, 2 H), 0.53 (m, 1H), 0.42 (m, 1H), 1.3 (t, J = 8.0 Hz, 3 H).
  • 2
  • [ 5239-82-7 ]
  • [ 302800-13-1 ]
  • [ 1447911-05-8 ]
YieldReaction ConditionsOperation in experiment
165 mg Example 15 1- (2- (Cyclopropylmethyl) -l-methyl-lH-benzimidazol-6-yl) -4- ( (4- fluorobenzyl) oxy) pyridin-2 ( 1H) -one A) 6-Bromo-2- (cyclopropylmethyl) -1-methyl-lH-benzimidazole Zinc (212 mg) was added to a mixture of 5-bromo-N-methyl- 2-nitroanilin.e (150 mg) , NH4C1 (347 mg) , eOH (2 ml) and water (1 ml) at room temperature. The mixture was stirred at room temperature for 1 h. After filtration and addition of saturated NaHC03 solution, the mixture was concentrated and extracted with AcOEt . The organic layer was separated, washed with brine, dried over MgS04 and concentrated in vacuo. To the resulting residue, DMF (2.0 ml), cyclopropylacetic acid (0.060 ml), N,N-diisopropylethylamine (0.339 ml) and HATU (259 mg) were added, and the mixture was stirred at room temperature for 1 h. The mixture was. quenched with brine and extracted with EtOAc twice. The organic layer was separated, washed with brine, dried over MgS04, passed through NH silica pad and concentrated in vacuo. The resulting residue was dissolved in AcOH (2.0 ml), and stirred at 80C for i h. After evaporation of the solvent, the residue was purified by NH silica gel column chromatography (hexane/EtOAc) to give the title compound (165 mg). as a purple gum. MS (ESI+) : [M+H] + 265.1.
  • 3
  • [ 5239-82-7 ]
  • [ 1200828-74-5 ]
  • 4
  • [ 5239-82-7 ]
  • [ 337915-79-4 ]
  • [ 1447911-04-7 ]
  • 5
  • [ 5239-82-7 ]
  • [ 337915-79-4 ]
  • [ 1447911-05-8 ]
YieldReaction ConditionsOperation in experiment
96% General procedure: HATU (4.89 g, 12.9 mmol) was added to a solution of the intermediate 4-bromo-N2-ethylbenzene-1,2-diamine, DIPEA (6.40 mL, 36.7 mmol), and cyclopropanecarboxylic acid (0.98 mL, 12.2 mmol) in DMF (40 mL), and the mixture was stirred at rt for 1 h. The mixture was quenched with water and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was dissolved in AcOH (40 mL) and the mixture was stirred at 80 C for 1 h. After concentration of the mixture, the residue was neutralized with satd NaHCO3 solution and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/EtOAc = 100/0 to 0/100) to give the title compound (1.2 g, 37%) as a pale yellow solid.
 

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