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Chemical Structure| 20430-18-6 Chemical Structure| 20430-18-6

Structure of 20430-18-6

Chemical Structure| 20430-18-6

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Product Details of [ 20430-18-6 ]

CAS No. :20430-18-6
Formula : C11H14O2
M.W : 178.23
SMILES Code : CC(C1=CC=C(C)C=C1)(C)C(O)=O
MDL No. :MFCD11036959
InChI Key :SHDBWXXRCCHGQD-UHFFFAOYSA-N
Pubchem ID :12369085

Safety of [ 20430-18-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H303-H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 20430-18-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 52.45
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.

1.69
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

2.68
Log Po/w (WLOGP)?

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

2.36
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.

2.58
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

2.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.34

Water Solubility

Log S (ESOL):?

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

-2.84
Solubility 0.256 mg/ml ; 0.00144 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.

-3.12
Solubility 0.137 mg/ml ; 0.000766 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

-2.98
Solubility 0.187 mg/ml ; 0.00105 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.

-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.

0.56

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)

1.21

Application In Synthesis of [ 20430-18-6 ]

* 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 [ 20430-18-6 ]

[ 20430-18-6 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 20430-18-6 ]
  • [ 24911-30-6 ]
  • 2
  • [ 32454-12-9 ]
  • [ 20430-18-6 ]
  • 3
  • [ 75920-47-7 ]
  • [ 20430-18-6 ]
  • 5
  • [ 64-17-5 ]
  • [ 20430-18-6 ]
  • [ 32454-24-3 ]
  • 6
  • [ 40119-34-4 ]
  • [ 20430-18-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; diethylene glycol; (2) Synthesis of 2-(4-Methylphenyl)-2-methylpropionic Acid A solution of 2-(4-methylphenyl)-2-methylpropionitrile (53.61 g), sodium hydroxide (40.4 g), diethylene glycol (160.8 ml) and water (60.6 ml) was refluxed for 18 hr. The reaction mixture was poured into water (3000 ml) and conc. hydrochloric acid (90 ml) was added. The generated crystals were collected by filtration to give the title compound (60.0 g) as pale-brown crystals, m.p.=78-81 C. 1H-NMR(CDCl3)δ: 1.57(6H, s), 2.32(3H, s), 7.14(2H, d, J=8.6 Hz), 7.28(2H, d, J=8.6 Hz). MS(EI): 178(M+).
With sulfuric acid; water; at 180℃; for 2h; Step B: Preparation of 2-Methyl-2-p-tolylpropanoic acid; [0742] 9M H2SO4 (65.0 mL) was added to 2-methyl-2-p- tolylpropanenitrile (6.21 g, 39.0 mmol). The reaction mixture was then heated at 1800C in a sealed tube for 2 hours. The reaction mixture was cooled to ambient temperature, diluted with 100 mL of diethyl ether, added to a separation funnel, washed with 5N HCl, partitioned with 5N NaOH (aqueous), washed 2 times with 20 mL of 5N NaOH (aqueous), and separated before the aqueous layer was acidified to pH = 3 with 3N HCl and extracted 3 times with 75 mL of diethyl ether, dried over Na2SO4, and concentrated in vacuo to give the title <n="170"/>compound (5.27 g) as brownish yellow amorphous solid. MS (m/z) = 180 (M+H)+.
  • 7
  • [ 20430-18-6 ]
  • [ 40919-17-3 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; at 65℃; for 1h; Step C: Preparation of Diethyl 2-(2-methyl-2-p- tolylpropanoyl)malonate; [0744] To a mixture of magnesium (1.08 g, 44.3 mmol) and diethyl malonate (6.70 mL, 44.3 mmol) were added EtOH (15.5 mL, 266 mmol) and CCl4 (0.21 mL) at ambient temperature. The reaction was controlled by slowly adding THF (44 mL). The reaction mixture was stirred at 700C for 1 hour and then allowed to cool. The acid chloride formed from 2-methyl-2-p- tolylpropanoic acid (5.27 g, 29.6 mmol; converted to the acid chloride by reaction with thionyl chloride at 65C for 1 hour, and then concentrating) was added dropwise as an ether solution via addition funnel. The resulting mixture was stirred for 30 minutes at ambient temperature and then quenched with 5N HCl. The mixture was diluted with 200 mL of diethyl ether, added to a separatory funnel, partitioned with water, washed 2 times with 75 mL of water, separated, dried over Na2SO4, and concentrated in vacuo to give the title compound (9.24 g) as a brown oil which was used without further purification. MS (m/z) = 321 (M+H)+.
  • 8
  • [ 14062-19-2 ]
  • [ 74-88-4 ]
  • [ 20430-18-6 ]
  • 9
  • [ 7647-01-0 ]
  • [ 7446-70-0 ]
  • [ 79-41-4 ]
  • [ 108-88-3 ]
  • [ 20430-18-6 ]
  • [ 29205-99-0 ]
  • [ 93351-25-8 ]
YieldReaction ConditionsOperation in experiment
B) 2-(para-Tolyl)-2-methylpropionic acid. 24.4 g of the compound prepared in the preceding stage in 1.44 1 of diethyl ethylene glycol and 1.88 1 of 40% aqueous potassium hydroxide are brought to reflux for 16 hours. The reaction mixture is diluted with water and then extracted with ether. The aqueous phase is acidified with concentrated hydrochloric acid, extracted with ethyl acetate, washed with water, dried over sodium sulphate and concentrated. The product obtained is chromatographed on silica by eluding with an AcOEt/hexane/acetic acid (20/80/1; v/v/v) mixture. 22 g of the expected product are collected.
  • 11
  • [ 64-17-5 ]
  • [ 32454-12-9 ]
  • Ag2O [ No CAS ]
  • [ 20430-18-6 ]
  • 14
  • [ 20430-18-6 ]
  • [ 19884-69-6 ]
  • 15
  • [ 20430-18-6 ]
  • 2,3-Dimethyl-3-(4-methyl-phenyl)-butanol-(2) [ No CAS ]
  • 16
  • [ 20430-18-6 ]
  • [ 68682-48-4 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In methanol; water; (3) Synthesis of Methyl 2-(4-Methylphenyl)-2-methylpropionate A solution of 2-(4-methylphenyl)-2-methylpropionic acid (60.0 g), sulfuric acid (0.6 ml) and methanol (300 ml) was refluxed for 19 hr. The solvent was evaporated, and water (200 ml) was added and the mixture was extracted with chloroform. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give the title compound (61.52 g) as a pale-brown oil. 1H-NMR(CDCl3)δ:1.56(6H, s), 2.32(3H, s), 3.64(3H, s), 7.13(2H, d, J=8.6 Hz), 7.22(2H, d, J=8.6 Hz). MS(EI): 192(M+).
  • 17
  • [ 20430-18-6 ]
  • [ 74-88-4 ]
  • [ 68682-48-4 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetone; at 20 - 50℃; for 3h; To a stirred mixture of Intermediate 28 (4.86 g, 26.5 mmol) and K2C03 (14.6 g, 106 mmol) in acetone (150 mL), methyl iodine (ALDRICH, 16 mL, 265 mmol) was added at room temperature, and, then, the reaction mixture was stirred at 50C for 3 hours. The mixture was filtered, the filtrate was evaporated to dryness, and the residue was chromatographed (silica gel, 1:1 hexane/ethyl acetate) to obtain 4.37 g of the desired product. 1H NMR (300 MHz, DMSO-d6) S ppm: 7.15 (m, 4H), 3.56 (s, 3H), 2.25 (s, 3H), 1.46 (s, 6H).
  • 18
  • [ 622-47-9 ]
  • [ 74-88-4 ]
  • [ 20430-18-6 ]
YieldReaction ConditionsOperation in experiment
To a solution of diisopropylamine (ALDRICH, 15.2 mL, 109 mmol) in 108 mL of anhydrous THF at -20C under N2 was added n-BuLi (55.7 mL, 106 mmol, 1.9M solution in hexane) droDwise via cannula. After stirrina for 2 hours. D-tolvlacetic acid (ALDRICH. 3.99 a. 26.5mmol) was added in 26 mL of THF. The mixture was stirred at -5C for 2 hours and, then, treated with iodomethane (9.9 mL, 159 mmol). The reaction mixture was allowed to gradually warm up to room temperature, stirred at that temperature for 15 hours, and then, quenched by pouring it into 20 mL of HCI (1N). The aqueous layer was extracted with Et20 (3x100 mL). The organic layer was treated with brine and dried over MgS04 and concentrated in vacuo to give 4.86 g of the title compound as a brown oil. 1H NMR (300 MHz, DMSO-d6) 8 ppm: 12.22 (br.s, 1H), 7.21 (m, 2H), 7.12 (m, 2H), 2.25 (s, 3H), 1.43 (s, 6H). No molecular peak is detected by MS.
  • 19
  • [ 20430-18-6 ]
  • [ 30313-83-8 ]
YieldReaction ConditionsOperation in experiment
60% With isopropylmagnesium bromide; triphenylphosphine; cobalt(II) chloride; In tetrahydrofuran; at 20℃; for 18h;Green chemistry; General procedure: The iPrMgBr (excess in THF) was added to a mixture of α,α-dimethyl phenylacetic acids (1 mmol), cobalt salt (10 mol%), ligand (20 mol%) in dried THF (3 mL), the reaction mixture was stirred at room temperature for 18 h. After that, the mixture was concentrated under vacuum and the residue was purified by column chromatography on silica gel with a gradient eluent of petroleum ether and dichloromethane to give the corresponding products.
  • 23
  • [ 74-83-9 ]
  • [ 938-94-3 ]
  • [ 20430-18-6 ]
  • 24
  • [ 20430-18-6 ]
  • [ 1581735-33-2 ]
  • 25
  • [ 20430-18-6 ]
  • [ 22115-41-9 ]
  • 2-cyanobenzyl 2-methyl-2-(p-tolyl)propanoate [ No CAS ]
  • 26
  • [ 20430-18-6 ]
  • ethyl (E)-3-(5-(1-((2-cyanobenzyl)oxy)-2-methyl-1-oxopropan-2-yl)-2-methylphenyl)acrylate [ No CAS ]
 

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