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Chemical Structure| 24398-88-7 Chemical Structure| 24398-88-7
Chemical Structure| 24398-88-7

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Ethyl 3-bromobenzoate

CAS No.: 24398-88-7

4.5 *For Research Use Only !

Cat. No.: A462527 Purity: 95%

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Product Details of [ 24398-88-7 ]

CAS No. :24398-88-7
Formula : C9H9BrO2
M.W : 229.07
SMILES Code : O=C(OCC)C1=CC=CC(Br)=C1
MDL No. :MFCD00013529
InChI Key :QAUASTLEZAPQTB-UHFFFAOYSA-N
Pubchem ID :90488

Safety of [ 24398-88-7 ]

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

Calculated chemistry of [ 24398-88-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 50.23
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.19
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

3.52
Log Po/w (WLOGP)?

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

2.63
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.

2.97
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

2.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.8

Water Solubility

Log S (ESOL):?

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

-3.65
Solubility 0.0513 mg/ml ; 0.000224 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.

-3.76
Solubility 0.0402 mg/ml ; 0.000175 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

-3.74
Solubility 0.0419 mg/ml ; 0.000183 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.

-5.2 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

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<2.0
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 [ 24398-88-7 ]

* 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.

  • Downstream synthetic route of [ 24398-88-7 ]

[ 24398-88-7 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 24398-88-7 ]
  • [ 63572-73-6 ]
  • C15H14N4O2 [ No CAS ]
  • 2
  • [ 24398-88-7 ]
  • [ 63572-73-6 ]
  • C15H12N4O4 [ No CAS ]
  • 3
  • [ 25475-67-6 ]
  • [ 24398-88-7 ]
  • [ 1370708-53-4 ]
YieldReaction ConditionsOperation in experiment
84% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; for 6h;Inert atmosphere; General procedure: A round-bottomed flask was charged with Pd2(dba)3 (5 mol percent ), ligand (10 molpercent), aryl halide (1mmol), appropriate isoquinolinamine (1 mmol), base (1.5 mmol) and dry solvent (5 mL). Theflask was flushed with argon for 5 min. The mixture was heated at reflux under magnetic stirring.After cooling down to room temperature, the reaction mixture was concentrated and the residuewas purified by flash column chromatography on silica gel.
  • 4
  • [ 24398-88-7 ]
  • [ 10601-99-7 ]
  • 5
  • [ 24398-88-7 ]
  • [ 22237-13-4 ]
  • ethyl 4'-ethoxybiphenyl-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; caesium fluoride; In 1,2-dimethoxyethane; at 80℃; for 7h;Inert atmosphere; Schlenk technique; Ethyl 4'-ethoxybiphenyl-3-carboxylate (3) A 20 mL Schlenk tube was dried under vacuum, filled with nitrogen and charged consecutively with 100.0 mg (70 μL, 0.437 mmol, 1.0 eq) ethyl-3-bromobenzoate, 72.5 mg (0.437 mmol, 1.0 eq) 4-ethoxyphenylboronic acid, 139.3 mg (0.917 mmol, 2.1 eq) CsF, 17.8 mg (0.022 mmol, 0.05 eq) PdCl2(dppf)*DCM and 5.0 mL DME. The orange suspension was degassed by vacuum/N2 cycles and stirred at 80 C. for 7 h. GC-MS analysis indicated full conversion (98% product) of the starting material. The reaction mixture was filtered through a pad of celite which was rinsed with EtOAc. The solvent from the filtrate was removed under reduced pressure and final purification by column chromatography (CH/EtOAc 15:1, size: 12.5*2.0 cm, 15 g silica gel) yielded the pure product. yield: 109.5 mg (93%); colorless solid; M.p.: 46-47 C.; Rf (CH/EtOAc 15:1): 0.40; 1H-NMR (300 MHz, CDCl3): δ (ppm)=δ (ppm)=8.25 (t, 4J=1.5 Hz, 1H, Ar-H), 7.98 (d, 3J=7.8 Hz, 1H, Ar-H), 7.74 (d, 3J=7.8 Hz, 1H, Ar-H), 7.56 (d, 3J=9.0 Hz, 2H, Ar-H), 7.48 (t, 3J=7.8 Hz, 1H, Ar-H), 6.98 (d, 3J=9.0 Hz, 2H, Ar-H), 4.41 (q, 3J=7.2 Hz, 2H, CH2), 4.09 (q, 3J=6.9 Hz, 2H, CH2), 1.47-1.39 (m, 6H, 2 CH3); 13C-NMR (75.5 MHz, CDCl3): δ (ppm)=166.6 (C=O), 158.8 (Cq), 141.0 (Cq), 132.5 (Cq), 131.0 (Cq), 130.9 (CHAr), 128.7 (CHAr), 128.2 (2 CHAr), 127.7 (CHAr), 127.6 (CHAr), 114.8 (2 CHAr), 63.8 (CH2), 61.0 (CH2), 14.8 (CH3), 14.3 (CH3); GC-MS (NM-50_S2): tR=7.796 min (m/z=270.1, 99% M+, BP); HRMS (EI+): m/z: calcd for C17H18O3 [M]+: 270.1256; found 270.1260.
93% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; caesium fluoride; In 1,2-dimethoxyethane; at 80℃; for 7h;Schlenk technique; Inert atmosphere; General procedure: A Schlenk tube was dried under vacuum, filled with nitrogen and charged consecutively with 1.00 eq bromine substrate, 1.00 eq boronic acid, 2.10 eq CsF, 0.05 eq PdCl2(dppf)*DCM and anhydrous DME (2 mL/0.15 mmol bromoarene). The suspension was degassed by vacuum/N2 cycles and stirred at 80 C. As TLC analysis or GC-MS analysis indicated full conversion of the starting material, the reaction mixture was cooled to rt and filtered through a pad of celite, which was rinsed with EtOAc and/or DCM. The solvent from the filtrate was removed under reduced pressure and final purification by column chromatography or silica gel filtration yielded the pure product.
  • 6
  • [ 24398-88-7 ]
  • [ 147404-69-1 ]
  • 7
  • [ 24398-88-7 ]
  • [ 108-36-1 ]
  • [ 25032-74-0 ]
YieldReaction ConditionsOperation in experiment
49% Under nitrogen, 1,3-dibromobenzene (30.0 g, 127 mmol)Was dissolved in THF (tetrahydrofuran)After dissolving in 300 mL, nBuLi (2.5M) 140 mmol, 56.0 mL was added and stirred at -78 C for 1 hourEthyl-3-bromobenzoate (26.2 g, 114 mmol) is added with a small amount of solvent. After 10 hours, the reaction mixture was slowly warmed to room temperature, quenched with NH4Cl, and extracted with ethyl acetate.The resulting organic solvent layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. This was subjected to column chromatography using ethyl acetate: hexane (EA: Hx) to obtain 21.0 g of [intermediate 1-1] (yield = 49%).
49% 1,3-Dibromobenzene (30.0 g, 127 mmol) was dissolved in 300 mL of THF (tetrahydrofuran) under nitrogen, 140 mmol of nBuLi (2.5 M) (56.0 mL) was added and stirred at -78 C for 1 hour. Ethyl 3-Bromobenzoate (26.2 g, 114 mmol) was added with a small amount of solvent. After 10 hours, the temperature was gradually raised to room temperature, and the residue was extracted with NH4Cl and extracted with ethyl acetate (EA). The resulting organic solvent layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. This was subjected to column chromatography with EA: Hx to obtain 21.0 g (yield = 49%) of [intermediate 1-1].
 

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