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Chemical Structure| 18305-60-7

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Product Details of [ 18305-60-7 ]

CAS No. :18305-60-7
Formula : C12H20O4
M.W : 228.29
SMILES Code : O=C(OC(C)(C)C)/C=C\C(OC(C)(C)C)=O
MDL No. :MFCD23381095
Boiling Point : No data available
InChI Key :MSVGHYYKWDQHFV-FPLPWBNLSA-N
Pubchem ID :5365124

Safety of [ 18305-60-7 ]

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

Computational Chemistry of [ 18305-60-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 61.97
TPSA ?

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

52.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.33
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

2.18
Log Po/w (WLOGP)?

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

2.23
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.

2.03
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

2.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.36

Water Solubility

Log S (ESOL):?

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

-2.23
Solubility 1.34 mg/ml ; 0.00585 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.

-2.92
Solubility 0.276 mg/ml ; 0.00121 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

-1.78
Solubility 3.81 mg/ml ; 0.0167 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.

-6.14 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

2.0 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)

2.66

Application In Synthesis of [ 18305-60-7 ]

* 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.

  • Upstream synthesis route of [ 18305-60-7 ]

[ 18305-60-7 ] Synthesis Path-Upstream   1~21

  • 1
  • [ 110-16-7 ]
  • [ 115-11-7 ]
  • [ 18305-60-7 ]
YieldReaction ConditionsOperation in experiment
75% With sulfuric acid In di-isopropyl ether; toluene at 40℃; for 4 h; General procedure: A 200 mL four-necked flask was charged with maleic acid (16.3 g, 140 mmol), toluene (10 mL)Diisopropyl ether (30 mL),Sulfuric acid (0.18 mL) was added, and while maintaining the reaction suspension at 30 ° C.,Normal pressure bubbling of isobutene was carried out for 4 hours.An excess amount of isobutene was discharged to the outside of the flask through a paraffin bubbler. The reaction mixture was washed with a saturated aqueous sodium hydrogen carbonate solution (50 mL × 3 times) and saturated brine (50 mL), dried over magnesium sulfate and the solvent was distilled off under reduced pressure to give maleic acid Di (tert-butyl) ester (23.0 g, 100.8 mmol, yield 72percent). The reaction was carried out in the same manner as in Example 1 except that the reaction temperature was changed from 30 ° C. to 40 ° C. As a result, maleic acid Di (tert-butyl) ester(24.1 g, 105.6 mmol, yield 75percent).
62% With toluene-4-sulfonic acid In 1,2-dimethoxyethane at 40℃; for 2 h; Autoclave 60 mL of ethylene glycol dimethyl ether represented by the general formula (1), 20 g of maleic acid and 4 g of p-toluenesulfonic acid as an acid catalyst were placed in a 300 mL autoclave equipped with a stirrer and a thermometer, 51 g of 2-methylpropylene was injected The reaction was carried out at 40 ° C. for 2 hours with stirring (255 parts by weight of 2-methylpropylene, 260 parts by weight of ethylene glycol dimethyl ether, 20 parts by weight of p-toluenesulfonic acid based on 100 parts by weight of maleic acid). As a result of GC analysis of the obtained reaction solution, the yield of di-tert-butyl maleate was 62percent.
References: [1] Patent: JP5754133, 2015, B2, . Location in patent: Paragraph 0063; 0065.
[2] Patent: JP5678489, 2015, B2, . Location in patent: Paragraph 0034; 0040.
[3] Tetrahedron Letters, 1995, vol. 36, # 41, p. 7459 - 7462.
[4] Acta Chemica Scandinavica (1947-1973), 1967, vol. 21, p. 1963 - 1964.
[5] Bulletin de la Societe Chimique de France, 1974, p. 2985 - 2986.
  • 2
  • [ 108-31-6 ]
  • [ 115-11-7 ]
  • [ 18305-60-7 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: With toluene-4-sulfonic acid In di-isopropyl ether; water; toluene at 30℃; for 2 h;
Stage #2: at 30℃; for 4 h;
To a 200 mL four-necked flask were placed maleic anhydride (13.7 g, 140 mmol), toluene (10 mL), diisopropyl ether (30 mL), water (2.78 mL), p-toluenesulfonic acid monohydrate After stirring at 30 ° C. for 2 hours, while maintaining the reaction suspension at 30 ° C., isobutene was bubbled under normal pressure for 4 hours. An excess amount of isobutene was discharged out of the flask through a paraffin bubbler. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate (3 × 50 mL) and saturated brine (50 mL), dried over magnesium sulfate and the solvent was distilled off under reduced pressure to give maleic acid Di (tert-butyl) ester (23.4 g, 102.5 mmol, yield 73percent).
References: [1] Patent: JP5754133, 2015, B2, . Location in patent: Paragraph 0075.
  • 3
  • [ 35059-50-8 ]
  • [ 18305-60-7 ]
References: [1] Chemistry - A European Journal, 2007, vol. 13, # 12, p. 3470 - 3479.
[2] Chemical Communications, 2005, # 39, p. 4902 - 4904.
  • 4
  • [ 292638-84-7 ]
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
  • [ 5279-78-7 ]
  • [ 5279-78-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
[2] Synlett, 1999, # 11, p. 1826 - 1828.
[3] Chemistry Letters, 2010, vol. 39, # 7, p. 702 - 703.
  • 5
  • [ 623-73-4 ]
  • [ 35059-50-8 ]
  • [ 18305-60-7 ]
  • [ 141-05-9 ]
References: [1] Chemistry - A European Journal, 2007, vol. 13, # 12, p. 3470 - 3479.
  • 6
  • [ 592-41-6 ]
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
  • [ 100207-44-1 ]
References: [1] Chemistry Letters, 2010, vol. 39, # 7, p. 702 - 703.
  • 7
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Chemistry Letters, 1994, # 6, p. 1111 - 1114.
  • 8
  • [ 66086-33-7 ]
  • [ 18305-60-7 ]
References: [1] Tetrahedron Letters, 2017, vol. 58, # 40, p. 3834 - 3837.
  • 9
  • [ 292638-84-7 ]
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
  • [ 105367-35-9 ]
References: [1] Synlett, 1999, # 11, p. 1793 - 1795.
  • 10
  • [ 35059-50-8 ]
  • [ 95-13-6 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
  • 11
  • [ 66086-33-7 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Tetrahedron Letters, 2017, vol. 58, # 40, p. 3834 - 3837.
  • 12
  • [ 35059-50-8 ]
  • [ 95-13-6 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
  • 13
  • [ 35059-50-8 ]
  • [ 98-83-9 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
  • 14
  • [ 292638-84-7 ]
  • [ 35059-50-8 ]
  • [ 18305-60-7 ]
  • [ 5279-78-7 ]
  • [ 105367-35-9 ]
  • [ 5279-78-7 ]
References: [1] Helvetica Chimica Acta, 1988, vol. 71, p. 1553 - 1565.
  • 15
  • [ 22136-61-4 ]
  • [ 35059-50-8 ]
  • [ 10099-70-4 ]
  • [ 18305-60-7 ]
References: [1] Chemistry - A European Journal, 2007, vol. 13, # 12, p. 3470 - 3479.
  • 16
  • [ 63254-54-6 ]
  • [ 35059-50-8 ]
  • [ 18305-60-7 ]
  • [ 621-13-6 ]
References: [1] Chemistry - A European Journal, 2007, vol. 13, # 12, p. 3470 - 3479.
  • 17
  • [ 35059-50-8 ]
  • [ 167693-38-1 ]
  • [ 18305-60-7 ]
References: [1] Chemistry - A European Journal, 2007, vol. 13, # 12, p. 3470 - 3479.
  • 18
  • [ 49653-47-6 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Journal of Organic Chemistry, 1990, vol. 55, # 1, p. 329 - 333.
[2] Journal of Organic Chemistry, 1990, vol. 55, # 1, p. 329 - 333.
  • 19
  • [ 110-87-2 ]
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
[2] Synlett, 1999, # 11, p. 1826 - 1828.
[3] Synlett, 1999, # 11, p. 1826 - 1828.
  • 20
  • [ 591-49-1 ]
  • [ 35059-50-8 ]
  • [ 7633-38-7 ]
  • [ 18305-60-7 ]
References: [1] Synlett, 1999, # 11, p. 1826 - 1828.
[2] Synlett, 1999, # 11, p. 1826 - 1828.
[3] Synlett, 1999, # 11, p. 1826 - 1828.
  • 21
  • [ 67-56-1 ]
  • [ 110-16-7 ]
  • [ 115-11-7 ]
  • [ 18305-60-7 ]
References: [1] Journal of Organic Chemistry, 1975, vol. 40, # 16, p. 2391 - 2394.
 

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