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Chemical Structure| 51716-63-3 Chemical Structure| 51716-63-3
Chemical Structure| 51716-63-3

cis-Tetrahydropentalene-2,5(1H,3H)-dione

CAS No.: 51716-63-3

4.5 *For Research Use Only !

Cat. No.: A132031 Purity: 97%

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Product Details of [ 51716-63-3 ]

CAS No. :51716-63-3
Formula : C8H10O2
M.W : 138.16
SMILES Code : O=C(C[C@@]1([H])C2)C[C@]1([H])CC2=O
MDL No. :MFCD00003771

Safety of [ 51716-63-3 ]

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

Calculated chemistry of [ 51716-63-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 36.74
TPSA ?

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

34.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

-0.35
Log Po/w (WLOGP)?

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

0.94
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.

0.65
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

1.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.86

Water Solubility

Log S (ESOL):?

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

-0.48
Solubility 46.2 mg/ml ; 0.334 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.

0.1
Solubility 172.0 mg/ml ; 1.24 mol/l
Class?

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

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

-1.39
Solubility 5.69 mg/ml ; 0.0412 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.

-7.39 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)

2.3

Application In Synthesis [ 51716-63-3 ]

* 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 [ 51716-63-3 ]

[ 51716-63-3 ] Synthesis Path-Downstream   1~27

  • 1
  • [ 917-64-6 ]
  • [ 51716-63-3 ]
  • 3,7-Dimethyl-cis-bicyclo<3.3.0>octan [ No CAS ]
  • 2
  • [ 917-64-6 ]
  • [ 51716-63-3 ]
  • 3,7-Dimethyl-cis-bicyclo<3.3.0>octan-3,7-diol [ No CAS ]
  • 4
  • [ 58648-36-5 ]
  • [ 51716-63-3 ]
YieldReaction ConditionsOperation in experiment
80% With hydrogenchloride; acetic acid; In water; for 3.5h;Reflux; Inert atmosphere; Step 2 (cis)- Bicyclo[3.3.0]octane-3,7-dione; (cis)-Tetramethyl bicyclo[3.3.0]octane-3,7-dioxo-2,4,6,8-tetracarboxylate 14b (6.75 g, 0.02 mol) was dissolved in 3.3 mL of acetic acid followed by the addition of 30 mL of 1 M hydrochloric acid. The reaction solution was heated to reflux for 3.5 hours and then cooled down to room temperature. The reaction solution was extracted with dichloromethane (50 mL×3). The combined orgnic phase was concentrated under reduced pressure, added with 100 mL of dichloromethane, added dropwise with saturated sodium bicarbonate solution to adjust pH to 7 and seperated. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (cis)-bicyclo[3.3.0]octane -3,7-dione 14c (2 g, yield: 80.0%) as a white solid.
80% Step 2 (cis)-Bicyclo[3.3.0]octane-3,7-dione (cis)-Tetramethyl bicyclo[3.3.0]octane-3,7-dioxo-2,4,6,8-tetracarboxylate 14b (6.75 g, 0.02 mol) was dissolved in 3.3 mL of acetic acid followed by the addition of 30 mL of 1 M hydrochloric acid. The reaction solution was heated to reflux for 3.5 hours and then cooled down to room temperature. The reaction solution was extracted with dichloromethane (50 mL*3). The combined organic phase was concentrated under reduced pressure, added with 100 mL of dichloromethane, added dropwise with saturated sodium bicarbonate solution to adjust pH to 7 and separated. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (cis)-bicyclo[3.3.0]octane-3,7-dione 14c (2g, yield: 80.0%) as a white solid.
  • 5
  • [ 556-56-9 ]
  • [ 102065-01-0 ]
  • [ 51716-63-3 ]
  • [ 102065-02-1 ]
  • 6
  • [ 18669-04-0 ]
  • [ 51716-63-3 ]
  • [ 89487-28-5 ]
  • 7
  • [ 18669-04-0 ]
  • [ 51716-63-3 ]
  • [ 89487-16-1 ]
  • 8
  • [ 51716-63-3 ]
  • [ 143-33-9 ]
  • [ 111717-99-8 ]
  • 9
  • [ 51716-63-3 ]
  • [ 151-50-8 ]
  • [ 111717-99-8 ]
  • 10
  • [ 51716-63-3 ]
  • [ 145448-46-0 ]
  • [ 145433-62-1 ]
  • [ 145433-61-0 ]
  • 11
  • [ 68703-09-3 ]
  • [ 51716-63-3 ]
  • 12
  • [ 51716-63-3 ]
  • [ 542-92-7 ]
  • [ 139607-41-3 ]
  • 13
  • [ 51716-63-3 ]
  • [ 107-21-1 ]
  • [ 51716-62-2 ]
YieldReaction ConditionsOperation in experiment
56% With toluene-4-sulfonic acid; In benzene;Heating / reflux; Preparation of 7,7-(ethylidene acetal)bicyclo[3.3.0] octane-3-one 1; bIn a 250 ml round bottom flask equipped with a water segregator, tetrahydro-pentalene-2,5-dione 1a (3 g, 21 mmol) and ethane-1,2-diol (1.03 mL, 18.5 mmol) were dissolved in 150 mL benzene under stirring, then 4-methylbenzenesulfonic acid (50 mg, 0.21 mmol) was added. Upon completion of the addition, the reaction mixture was heated to reflux overnight and then cooled to room temperature. The solvent of benzene was removed under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound 7,7-(ethylidene acetal)bicyclo[3.3.0] octane-3-one 1b (1.8 g, yield 56%) as a colorless oil.MS m/z (ESI): 183.5 [M+1].
40% With toluene-4-sulfonic acid; In toluene; at 100℃; for 10h; To (3as, 6as) -tetrahydropentadiene-2,5 (1H, 3H) -dione 1a (100 g, 725 mmol), ethylene glycol (40.4 g, 652 mmol), to the mixture with toluene (1.6 L), p-toluenesulfonic acid (12.4 g, 72.4 mmol) was added and the reaction mixture was heated to 100 C and stirred for 10 hours. Cool to room temperature and remove the solvent under reduced pressure. The residue was added with water and extracted with ethyl acetate (500 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered to remove the drying agent, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3/1) to obtain the target product (3aR,6aS)-tetrahydro-1H-spiro[pentalene-2,2'-[1,3]dioxolane]-5(3H)-one 1b (53 g, yellow oil), yield: 40%.
With toluene-4-sulfonic acid; In toluene; at 130℃; for 3h; Step 1 : To a solution of (3as,6as)-tetrahydropentalene-2,5(1 y,3H)-dione (500 mg, 3.62 mmol) in toluene (60 mL) was added ethylene glycol (226 mg, 3.65 mmol) and TsOH (20 mg) and the mixture was stirred at 130C for 3h, diluted with water and extracted with EtOAc. The organic portion was washed with brine, dried over Na2S04, filtered and concentrated to give (3a'R,6a'S)- tetrahydro-1 '/-/-spiro[[1 ,3]dioxolane-2,2'-pentalen]-5'(3'/-/)-one lnt-11a-1
  • 14
  • [ 51716-63-3 ]
  • [ 107-21-1 ]
  • [ 69552-45-0 ]
  • 15
  • [ 51716-63-3 ]
  • [ 108-98-5 ]
  • [ 139462-73-0 ]
  • [ 139462-72-9 ]
  • 17
  • [ 82416-02-2 ]
  • [ 51716-63-3 ]
  • 18
  • [ 68703-09-3 ]
  • [ 51716-63-3 ]
  • 19
  • [ 102065-01-0 ]
  • [ 51716-63-3 ]
  • 20
  • [ 51716-63-3 ]
  • [ 126-30-7 ]
  • [ 112755-94-9 ]
YieldReaction ConditionsOperation in experiment
66% With pyridinium p-toluenesulfonate; In toluene;Dean-Stark; Reflux; Inert atmosphere; To a solution of <strong>[51716-63-3](3as,6as)-tetrahydropentalene-2,5(1H,3H)-dione</strong> (15 g, 108.57 mmol) in toluene (150 mL) was added 2, 2-dimethylpropane-1,3-diol (11.31 g, 108.57 mmol), followed by the addition of PPTS (250 mg) at rt. The reaction mixture was refluxed overnight with a Dean-Stark trap under N 2 atmosphere. After cooled to rt, the reaction mixture was concentrated under vacuum to remove the volatile. The residue was purified by silica gel flash column chromatography (PE: EtOAc = 20: 1) to give the title compound (16 g, yield: 66%) as a white solid.
  • 22
  • [ 51716-63-3 ]
  • [ 107-18-6 ]
  • [ 114057-84-0 ]
  • [ 114057-86-2 ]
  • 24
  • [ 51716-63-3 ]
  • [ 882-33-7 ]
  • 2,6-bisphenylthio-cis-bicyclo<3.3.0>octane-3,7-dione [ No CAS ]
  • 25
  • [ 51716-63-3 ]
  • [ 931-59-9 ]
  • [ 89074-10-2 ]
  • 26
  • [ 51716-63-3 ]
  • [ 1885-29-6 ]
  • cis-6,6a,7,13a-tetra-hydropentaleno<2,1-b:5,4-b'>diquinoline-7,14-diamine [ No CAS ]
  • cis-6,6a,7,13b-tetra-hydropentaleno<2,1-b:5,4-b'>diquinoline-13,14-diamine [ No CAS ]
  • 27
  • [ 51716-63-3 ]
  • [ 145448-46-0 ]
 

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