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Chemical Structure| 52787-14-1 Chemical Structure| 52787-14-1

Structure of 52787-14-1

Chemical Structure| 52787-14-1

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Product Details of [ 52787-14-1 ]

CAS No. :52787-14-1
Formula : C11H12O4
M.W : 208.21
SMILES Code : O=C(OC)C1=CC=C(CC(OC)=O)C=C1
MDL No. :MFCD07779210
Boiling Point : No data available
InChI Key :QAQYBHOZQQRJBA-UHFFFAOYSA-N
Pubchem ID :10536335

Safety of [ 52787-14-1 ]

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

Computational Chemistry of [ 52787-14-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.27
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 53.59
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.

2.48
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

2.12
Log Po/w (WLOGP)?

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

1.19
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.

1.84
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

1.99
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.92

Water Solubility

Log S (ESOL):?

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

-2.43
Solubility 0.769 mg/ml ; 0.00369 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.

-2.86
Solubility 0.29 mg/ml ; 0.00139 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

-2.96
Solubility 0.228 mg/ml ; 0.00109 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

Yes
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.

-6.06 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

1.0 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)

1.62

Application In Synthesis of [ 52787-14-1 ]

* 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 [ 52787-14-1 ]

[ 52787-14-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 52787-14-1 ]
  • [ 22744-12-3 ]
YieldReaction ConditionsOperation in experiment
94.4% With lithium hydroxide monohydrate; water; In tetrahydrofuran; ethanol; at 25℃; for 10h; 2- (4- (methoxycarbonyl) phenyl) acetic acid (58,24.04 dirty 1) to the reaction flask, 31111 water, 31111 5ml tetrahydrofuran and a mixed solvent of ethanol raw materials were dissolved. Was then added Eta0Eta-Eta20 (1.068,25.24pipiomicron1) alpha25 C was stirred for 10 hours the reaction is substantially complete. The solution was spin-off in tetrahydrofuran and ethanol, followed by addition of 26ml of dilute hydrochloric acid (lmmol / L), and a white precipitate formed, suction, infrared drying to give a white solid 4.4g, 94.4% yield
83% With potassium carbonate; In methanol; water; at 20℃; for 4h; A solution of methyl 4- (2-methoxy-2-oxoethyl) benzoate 26, (800 mg, 3.85 ramol) and K2CO3 (929 mg, 5.67 mmol) in water/methanol mixture (20 mL, 1:1) was stirred at room temperature 4 hrs. After concentrating the reaction mixture to 5 mL diluted with water (20 mL) . Then the aqueous layer was washed with dichloromethane (20 mL chi 2), and acidified to pH~3 with 12M HC1. The aqueous solution was extracted with ethyl acetate (20 mL * 2) . Organics was combined, dried over NaaSOi and evaporated in vacuo to give titled compound 27. (620 mg, 83%). NMR (CHCI3, 400 MHz): delta 7.90 (d, J=8.1 Hz, 1H), 7.42 (d, J=8.1, 1H) , 3.85 (s, 3H) , 3.68 (s, 2H) ; [M+H]+ = 195.4 (APCI+) .
80% With hydrogenchloride; In methanol; at 20 - 50℃; for 28h; Step 2: 2-(4-(Methoxycarbonyl)phenyl)acetic Acid A stirred solution of methyl 4-(cyanomethyl)benzoate (22.0 g, 0.125 mol) in methanol (550 mL) was bubbled through with hydrogen chloride gas for 8 h under reflux conditions. The reaction mixture was cooled to 20 C., stirred for an additional 24 h and filtered. The filtrate was evaporated under reduced pressure. The resultant residue was dissolved in diethyl ether, washed sequentially with water and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and evaporated to afford the methyl ester as a solid residue. 1H NMR (400 MHz, CDCl3): 8.00 (d, J=8 Hz, 2H); 7.35 (d, J=8.4 Hz, 2H); 3.91 (s 3H); 3.70 (s, 3H); 3.68 (s, 2H). GCMS: 209 (M+H). The methyl ester (8.21 g, 0.039 mmol) was dissolved in methanol, treated with sodium hydroxide (1.58 g, 0.039 mol), heated to 50 C., stirred for 4 h, cooled to room temperature, stirred for an additional 24 h and concentrated in vacuo. The resultant residue was partitioned between diethyl ether and water. The aqueous layer was acidified with concentrated HCl. The resultant precipitate was removed by filtration and dried overnight, under vacuum, to afford 2-(4-(methoxycarbonyl)phenyl)-acetic acid (80%) as an off-white solid. 1H NMR (400 MHz, DSMO-d6): 7.90 (d, J=8 Hz, 2H); 7.422 (d, J=8 Hz, 2H); 3.85 (s 3H) 3.68 (s, 2H). [M+H] 195
64.4% With potassium carbonate; In methanol; water; at 20℃; for 1.5h; Methyl 4-(2-methoxy-2-oxoethyl)benzoate (100 mg, 0.48 mmol), methanol (1.5 mL), water (1.5 mL) and anhydrous potassium carbonate (116 mg, 0.72 mmol) were added in a 10 mL single-neck flask, and the mixture was stirred at room temperature for 1.5 hours. After the materials had all reacted when being determined by TLC, solvent was removed in vacuo, and the residue was redissolved in ethyl acetate (1 mL) and separated by preparative thin layer chromatography (petroleum ether: ethyl acetate = 1:1) to give a product (white solid, 60 mg), with a yield of 64.4%. 1H NMR (400 MHz, CDCl3) delta 8.00 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 3.91 (s, 3H), 3.70 (s, 2H).
With lithium hydroxide; In tetrahydrofuran; methanol; water; iv. 4-Methoxycarbonylphenylacetic acid. To a solution of methyl 4-methoxycarbonylphenylacetate (3.15 g) dissolved in tetrahydrofuran (100 mL), methanol (25 mL) and water (25 mL) at 0 C. was added lithium hydroxide (0.7 g) and the solution was allowed to stir for 2 h. The solution was acidified to pH 2.5 and the product extracted into ethyl acetate. The organic layer was dried (MgSO4) and evaporated to give an oil which was crystallized from hexane to give the mono-acid; TLC: Rf =0.65, methanol:dichloromethane (20:80); MS: m/z=195(M+1).
A stirred solution of methyl 4-(cyanomethyl)benzoate (22.0 g, 0.125 mol) in methanol (550 mL) was bubbled through with hydrogen chloride gas for 8 h under reflux conditions. The reaction mixture was cooled to 20 C., stirred for an additional 24 h and filtered. The filtrate was evaporated under reduced pressure. The resultant residue was dissolved in diethyl ether, washed sequentially with water and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and evaporated to afford the methyl ester as a solid residue. 1H NMR (400 MHz, CDCl3): 8.00 (d, J=8 Hz, 2H); 7.35 (d, J=8.4 Hz, 2H); 3.91 (s 3H); 3.70 (s, 3H); 3.68 (s, 2H). GCMS: 209 (M+H). The methyl ester (8.21 g, 0.039 mmol) was dissolved in methanol, treated with sodium hydroxide (1.58 g, 0.039 mol), heated to 50 C., stirred for 4 h, cooled to room temperature, stirred for an additional 24 h and concentrated in vacuo. The resultant residue was partitioned between diethyl ether and water. The aqueous layer was acidified with concentrated HCl. The resultant precipitate was removed by filtration and dried overnight, under vacuum, to afford 2-(4-(methoxycarbonyl)phenyl)-acetic acid (80%) as an off-white solid. 1H NMR (400 MHz, DSMO-d6): 7.90 (d, J=8 Hz, 2H); 7.422 (d, J=8 Hz, 2H); 3.85 (s 3H) 3.68 (s, 2H). [M+H] 195

 

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