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Chemical Structure| 5768-39-8

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Product Details of [ 5768-39-8 ]

CAS No. :5768-39-8
Formula : C8H6O4
M.W : 166.13
SMILES Code : O=C(C1=C2OCOC2=CC=C1)O
MDL No. :MFCD01076411
InChI Key :DBUAYOWCIUQXQW-UHFFFAOYSA-N
Pubchem ID :304832

Safety of [ 5768-39-8 ]

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

Computational Chemistry of [ 5768-39-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 39.46
TPSA ?

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

55.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

1.26
Log Po/w (WLOGP)?

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

1.11
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.

0.75
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

1.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.14

Water Solubility

Log S (ESOL):?

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

-1.97
Solubility 1.79 mg/ml ; 0.0108 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.

-2.03
Solubility 1.55 mg/ml ; 0.00934 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

-1.52
Solubility 5.06 mg/ml ; 0.0305 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.

-6.42 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)

2.1

Application In Synthesis of [ 5768-39-8 ]

* 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.

  • Upstream synthesis route of [ 5768-39-8 ]

[ 5768-39-8 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 33842-16-9 ]
  • [ 5768-39-8 ]
YieldReaction ConditionsOperation in experiment
97% With potassium hydroxide In methanol; water at 20℃; for 3 h; A solution of methyl benzo[ ][1 ,3]dioxole-4-carboxylate (0.4 g, 2.22 mmol) in methanol (8.0 mL) was treated with 2.0 M aqueous KOH (2.2 mL) and the solution stirred at rt for 3 hours. The mixture was concentrated to ~3 mL volume, diluted with water (5 mL) and acidified to pH ~3 using 2.0 M HCI. The resulting precipitate was removed by filtration, washed with water then diethyl ether and dried in vacuo to give benzo[ ][1 ,3]dioxole-4-carboxylic acid as a beige solid (0.38 g, 97percent).1H NMR (400 MHz, DMSO-d6): δ = 7.28 (dd, J= 8.0, 1.2 Hz, 1H),6.97 (dd, J=8.0, 1.2 Hz, 1H),6.89 (t, J=8.0Hz, 1 H), 6.12 (s, 2H);13C NMR(100 Hz, DMSO-de) 165.5, 148.9, 148.5, 122.9, 121.6, 113.8, 112.5, 102.1.
61% at 50℃; for 5 h; Compound P-2 (500 mg, 2.8 mmol) was weighed and suspended in 5 mL of water. Add 2N NaOH aqueous solution 10mL, Heat to 50°C for about 5 hours, The reaction solution is clear. Pour the reaction solution into ice water, Adjust pH to acidic with 2N dilute HCl There is a solid precipitated, Filtering, Dry powder 280mg, Yield 61percent. Used for the next reaction without purification.
References: [1] Patent: WO2016/131098, 2016, A1, . Location in patent: Page/Page column 167; 168; 169.
[2] Steroids, 2010, vol. 75, # 12, p. 967 - 973.
[3] Journal of Agricultural and Food Chemistry, 2011, vol. 59, # 2, p. 635 - 644.
[4] European Journal of Medicinal Chemistry, 2017, vol. 140, p. 604 - 614.
[5] Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 871 - 887.
[6] Patent: CN104016960, 2018, B, . Location in patent: Paragraph 0084-0087; 0094-0096.
[7] Patent: WO2004/4732, 2004, A1, . Location in patent: Page/Page column 66.
[8] Patent: WO2004/5284, 2004, A1, . Location in patent: Page 68.
  • 2
  • [ 23158-06-7 ]
  • [ 5768-39-8 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With water; sodium hydroxide In methanol at 20℃; for 3.5 h;
Stage #2: With hydrogenchloride In methanol; water
To a solution of the compound of the previous step (16 g) in methanol (170 ml) was added a solution of sodium hydroxide (9.9 g) in water (40 ml), and the mixture was stirred at room temperature for 3.5 hr.
The reaction solution was acidified with concentrated hydrochloric acid, and the mixture was concentrated.
The resulting precipitate was collected by filtration to give the title compound (13 g, 95percent).
NMR(300MHz, CDCl3)δ:6.14(2H, s), 6.90(1H, t, J=7.8Hz), 7.03(1H, dd, J=7.5, 1.2Hz), 7.46(1H, dd, J=8.1, 1.2Hz).
References: [1] Patent: EP2116538, 2009, A1, . Location in patent: Page/Page column 49.
  • 3
  • [ 7797-83-3 ]
  • [ 5768-39-8 ]
YieldReaction ConditionsOperation in experiment
96% With dihydrogen peroxide; potassium carbonate In methanol; water 2,3-(methylenedioxy)benzoic acid
A solution of 2,3-(methylenedioxy)benzaldehyde (160mg, 1.06mmol), potassium carbonate (960 mg, 6.9 mmol) and 2.4mL of hydrogen peroxide (30-32 wt.percent solution in water) in 10 mL of methanol was stirred for 16 hours at room temperature.
The mixture was washed with diethyl ether.
The water layer was acidified with 1 N aq. HCl to pH>1, then extracted with ethyl acetate.
The organic layer was dried over MgSO4, then concentrated to give the desired product (170mg, 96percent). EI-MS (m/z) 164.8 (M-).
References: [1] Patent: US6500863, 2002, B1, .
[2] Agricultural and Biological Chemistry, 1980, vol. 44, # 2, p. 235 - 243.
[3] Patent: US6303593, 2001, B1, .
  • 4
  • [ 274-09-9 ]
  • [ 5768-39-8 ]
References: [1] Patent: US5886044, 1999, A, .
[2] Patent: US5780483, 1998, A, .
[3] Patent: US6262113, 2001, B1, .
  • 5
  • [ 274-09-9 ]
  • [ 124-38-9 ]
  • [ 5768-39-8 ]
  • [ 120-80-9 ]
References: [1] Chemistry - A European Journal, 2002, vol. 8, # 4, p. 799 - 804.
  • 6
  • [ 2411-83-8 ]
  • [ 5768-39-8 ]
References: [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 871 - 887.
[2] Journal of Agricultural and Food Chemistry, 2011, vol. 59, # 2, p. 635 - 644.
[3] Patent: WO2016/131098, 2016, A1, .
[4] European Journal of Medicinal Chemistry, 2017, vol. 140, p. 604 - 614.
[5] Patent: CN104016960, 2018, B, .
  • 7
  • [ 303-38-8 ]
  • [ 5768-39-8 ]
References: [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 871 - 887.
[2] Journal of Agricultural and Food Chemistry, 2011, vol. 59, # 2, p. 635 - 644.
[3] Patent: WO2016/131098, 2016, A1, .
[4] Patent: CN104016960, 2018, B, .
  • 8
  • [ 254973-61-0 ]
  • [ 769-30-2 ]
  • [ 5768-39-8 ]
References: [1] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 21, p. 3133 - 3137.
  • 9
  • [ 24677-78-9 ]
  • [ 5768-39-8 ]
References: [1] Agricultural and Biological Chemistry, 1980, vol. 44, # 2, p. 235 - 243.
  • 10
  • [ 148-53-8 ]
  • [ 5768-39-8 ]
References: [1] Agricultural and Biological Chemistry, 1980, vol. 44, # 2, p. 235 - 243.
  • 11
  • [ 1521-38-6 ]
  • [ 5768-39-8 ]
References: [1] Journal of the Chemical Society, 1926, p. 2932.
  • 12
  • [ 86-51-1 ]
  • [ 5768-39-8 ]
References: [1] Journal of the Chemical Society, 1926, p. 2932.
  • 13
  • [ 75-11-6 ]
  • [ 303-38-8 ]
  • [ 5768-39-8 ]
References: [1] Journal of the Chemical Society, 1926, p. 2932.
  • 14
  • [ 769-30-2 ]
  • [ 5768-39-8 ]
References: [1] RSC Advances, 2016, vol. 6, # 108, p. 106769 - 106777.
 

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