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Chemical Structure| 7588-36-5 Chemical Structure| 7588-36-5

Structure of 7588-36-5

Chemical Structure| 7588-36-5

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Product Details of [ 7588-36-5 ]

CAS No. :7588-36-5
Formula : C13H15NO3
M.W : 233.26
SMILES Code : O=C(OC)CC1=C(C)NC2=C1C=C(OC)C=C2
MDL No. :MFCD00218549
InChI Key :JYUNCKSXPPDNRM-UHFFFAOYSA-N
Pubchem ID :82067

Safety of [ 7588-36-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 7588-36-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 9
Fraction Csp3 0.31
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 65.62
TPSA ?

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

51.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.39
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

2.21
Log Po/w (WLOGP)?

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

2.2
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.

1.37
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

3.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.28

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.364 mg/ml ; 0.00156 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 0.279 mg/ml ; 0.0012 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

-4.29
Solubility 0.012 mg/ml ; 0.0000516 mol/l
Class?

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

Moderately 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.

-6.15 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.

1.0 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)

2.03

Application In Synthesis of [ 7588-36-5 ]

* 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 [ 7588-36-5 ]

[ 7588-36-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 67-56-1 ]
  • [ 2882-15-7 ]
  • [ 7588-36-5 ]
YieldReaction ConditionsOperation in experiment
100% General procedure: A reaction mixture containing the indoleacetic acid derivative (1 equivalent) and BOP-Cl (1 equivalent) in 3 mL/mmol of anhydrous CH2Cl2 is treated with triethylamine (2 equivalents) and aged at ambient temperature for 5 min. The mixture is combined with anhydrous methanol (0.14 mL/mmol) and then continuously stirred overnight at room temperature. Following dilution with dichloromethane (12 mL/mmol), the organic solution is washed with water (2x6 mL/mmol), dried over Na2SO4, and filtered. The organic filtrate is collected and concentrated in vacuo and the crude ester is purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to afford the title compound at first as viscous yellow oil, which stably crystallizes upon seeding and subsequent cold storage.
83% With chloro-trimethyl-silane; at 20℃; General procedure: Indomethacin (3.00 g, 8.39 mmol) was dissolved in 1 M NaOH(200 mL) and left to stir overnight. The reaction was acidified with1 M HCl and the precipitate filtered off. Filtrate was then extractedthree times with DCM (100 mL). Combined organic layer was driedover Na2SO4 and concentrated in vacuo to give crude 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.12 g, 5.15 mmol). Thecrude intermediate was dissolved in MeOH (50 mL) and TMSCl(1.86 mL, 14.73 mmol) was added. The reaction mixture was leftto stir at room temperature overnight. Water (50 mL) was addedto quench the reaction and extracted three times with DCM(50 mL). Organic layer was combined, dried over Na2SO4 and concentratedin vacuo. Residue obtained was purified by column chromatographyusing CHCl3:EtOAc (10:1) to give 12 as a brown solid(0.99 g, 83%). 1H NMR (400 MHz, CDCl3) d 7.92 (s, 1H), 7.07 (d,J = 8.7 Hz, 1H), 7.01 (d, J = 2.0 Hz, 1H), 6.81-6.75 (m, 1H), 3.87 (d,J = 1.1 Hz, 3H), 3.68 (d, J = 1.0 Hz, 5H), 2.32 (s, 3H). 13C NMR(101 MHz, CDCl3) d 172.8, 154.1, 133.7, 130.2, 129.0, 111.1,110.8, 104.1, 100.4, 55.9, 51.9, 30.3, 11.7.
  • 2
  • [ 2882-15-7 ]
  • [ 7588-36-5 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In methanol; ethyl acetate; A. 5-Methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. A solution of 12.2 g (0.0557 mol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid in 150 mL of MeOH and 1 mL of sulfuric acid was heated to maintain reflux for 15 hours. After cooling, the mixture was diluted with sodium bicarbonate solution and extracted with EtOAc. The EtOAc solution was washed with saturated NaCl solution and dried (Na2 SO4). The solvent was removed at reduce pressure to give 13 g of crude 5-methoxy-2-methyl-1H-indole-3-acetic acid methyl ester.
With sulfuric acid; In methanol; ethyl acetate; A. 5-Methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. A solution of 12.2 g (0.0557 mol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid in 150 of MeOH and 1 ml of sulfuric acid was heated to maintain reflux for 15 hours. After cooling, the mixture was diluted with a sodium bicarbonate solution and extracted with EtOAc. The EtOAc solution was washed with a saturated NaCl solution and dried (Na2 SO4). The solvent was removed at reduced pressure to give 13 g of crude 5-methoxy-2-methyl-1H-indole-3-acetic acid methyl ester.
With sodium hydroxide; sulfuric acid; In methanol; dichloromethane; Step 1 Methyl 5-methoxy-2-methylindole-3-acetate. To a solution of 5-methoxy-2-methylindole-3-acetic acid (10 g, 45.6 mmol) in 100 mL of methanol was added 10 drops of concentrated sulfuric acid. The reaction mixture was heated at reflux for 2 h then cooled to room temperature. The pH was adjusted to approximately or about 7 using 1N NaOH. The solvent was removed under reduced pressure. The yellow oily residue was dissolved in methylene Chloride and filtered through a plug of silica gel using 2% methanol/CH2 Cl2. The solvent was removed to give 10.6 g (quantitative) of the methyl ester as a yellow oil.
  • 3
  • [ 2882-15-7 ]
  • [ 75-36-5 ]
  • [ 7588-36-5 ]
 

Historical Records

Technical Information

Categories

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[ 7588-36-5 ]

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[ 7588-36-5 ]

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