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Chemical Structure| 1462-37-9 Chemical Structure| 1462-37-9

Structure of Benzyl 2-bromoethyl ether
CAS No.: 1462-37-9

Chemical Structure| 1462-37-9

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Product Citations

Product Citations

Senevirathne, Priyangika Prasadini ;

Abstract: Reactive oxygen species are a group of highly reactive oxygen-containing entities that are important at a cellular level for multiple biological processes. Low concentrations of ROS can be beneficial as powerful signaling molecules in those biological processes, although excessive concentrations can promote high levels of DNA damage and a variety of diseases such as skin cancer. A newly identified intracellular ROS production source in skin cells is NADPH oxidases. Out of the NOX enzyme family, the NOX1 holoenzyme is most abundantly expressed in the human keratinocyte cells. UV radiation can trigger the activation of NOX1 isoforms which stimulate the assembling of member CYBA and the cytoplasmic protein NOXO1. Inhibition of these enzymes represents a catalytic approach toward reducing ROS for the prevention of ROS inducible diseases. Key disease states include melanoma induced by UV exposure. The first half of the dissertation focuses on investigating new small molecule inhibitors of a key NOX1 holoenzyme to address these challenges. We designed a series of molecules by optimizing the structure of diapocynin and evaluated by in-silico docking methods to determine the binding affinity with NOXO1 cytoplasmic protein (1WLP crystal structure). And have synthesized the series of target molecules for the structure-activity relationship studies. In the first section of the project, we discovered that inhibitor NOX_inh_5 was not cytotoxic, but instead improved the viability of human primary cells from UV exposure, decreased the cellular stress in human skin through the p53 pathway, and reduced the UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation after UV exposure. Then, we characterized the inhibition potential of NOX_inh_5 by using an Isothermal calorimetric (ITC) binding assay and heteronuclear single quantum coherence (HSQC) technique and revealed that the candidate iii molecule can prevent the complex formation of NOXO1 and CYBA membrane protein. In the second section of the project, we did a structure-activity relationship study for the NOX_inh_5 small molecule to optimize the biological characteristics. The last section of the dissertation discussed the development of ROS sensible prodrug to combat the opioid overdose crisis. Here we used oxidative stress conditions caused by opioid overdose to activate the prodrug. Even though opioid antagonist naloxone has a high affinity to bind with opioid receptors to block opioid-induced activation, it is metabolically unstable and has a short half-life of around 33 min. We developed a peroxide-induced prodrug to overcome this issue that can release a steady stream of naloxone. This allows the concentration of naloxone to remain high for longer periods.

Alternative Products

Product Details of [ 1462-37-9 ]

CAS No. :1462-37-9
Formula : C9H11BrO
M.W : 215.09
SMILES Code : BrCCOCC1=CC=CC=C1
MDL No. :MFCD01321307
InChI Key :FWOHDAGPWDEWIB-UHFFFAOYSA-N
Pubchem ID :73833

Safety of [ 1462-37-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H318-H335-H411
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P362+P364-P403+P233-P501
Class:9
UN#:3334
Packing Group:

Computational Chemistry of [ 1462-37-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 4
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 49.98
TPSA ?

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

9.23 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

2.55
Log Po/w (WLOGP)?

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

2.45
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.

2.64
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

3.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.61

Water Solubility

Log S (ESOL):?

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

-2.92
Solubility 0.259 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 (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.39
Solubility 0.874 mg/ml ; 0.00406 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

-4.21
Solubility 0.0132 mg/ml ; 0.0000615 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

Yes
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.

-5.8 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.

0.55

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)

1.76

Application In Synthesis of [ 1462-37-9 ]

* 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 [ 1462-37-9 ]

[ 1462-37-9 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 1462-37-9 ]
  • [ 95656-88-5 ]
  • [ 1404531-44-7 ]
YieldReaction ConditionsOperation in experiment
With tetra-(n-butyl)ammonium iodide; sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 80℃; A solution of 1.29 g of <strong>[95656-88-5]benzyl 3-hydroxypyrrolidine-1-carboxylate</strong> in 80 ml of THF is cooled to 0 C., 0.245 g of 60% NaH in oil is added and then 1.26 g of [(2-bromoethoxy)methyl]benzene and 0.108 g of tetrabutylammonium iodide and it is heated at 80 C. for 3 hours. 0.28 g of NaH and 0.40 g of [(2-bromoethoxy)methyl]benzene are added and it is heated at 80 C. for 2 hours. The reaction mixture is concentrated under vacuum, the residue is extracted with DCM, the organic phase is washed with 0.1M HCl solution, with a saturated solution of NaHCO3, it is dried and the solvent is evaporated under vacuum. The product thus obtained is purified by preparative HPLC and 0.46 g of the expected compound is obtained.
With tetra-(n-butyl)ammonium iodide; sodium hydride; In tetrahydrofuran; oil; at 80℃; for 5h; Preparation 7.92-(Pyrrolidin-3-yloxy)ethanol.Step 1 : Benzyl 3-(2-benzyloxyethoxy)pyrrolidine-1 -carboxylate.A solution of 1 .29 g of benzyl 3-hydroxypyrrolidine-1 -carboxylate in 80 ml of THF is cooled to 0C, 0.245 g of 60% NaH in oil is added and then 1 .26 g of [(2- bromoethoxy)methyl]benzene and 0.108 g of tetrabutylammonium iodide and it is heated at 80C for 3 hours. 0.28 g of NaH and 0.40 g of [(2- bromoethoxy)methyl]benzene are added and it is heated at 80C for 2 hours. The reaction mixture is concentrated under vacuum, the residue is extracted with DCM, the organic phase is washed with 0.1 M HCI solution, with a saturated solution of NaHC03, it is dried and the solvent is evaporated under vacuum. The product thus obtained is purified by preparative HPLC and 0.46 g of the expected compound is obtained.
  • 2
  • [ 1123-93-9 ]
  • [ 1462-37-9 ]
  • C16H16N2OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
285 mg To a stirred solution of benzo[cf]thiazol-5-amine (250 mg, 1.66 mmol) in acetonitrile (5 mL) were added the K2CO3 (276 mg, 2.00 mmol) in portion wise over the period of 10 min at 0 °C and the reaction mixture heated at 65 °C for 30 min. Then the temperature was brought to 30 °C, ((2-bromoethoxy)methyl)benzene (0.290 mL, 1.83 mmol) was added the resulting reaction mixture was refluxed for 24h. The reaction mixture was concentrated to dryness; the crude material dissolved in water (30 mL), washed with ether (2 x 30 mL) to remove organic impurities and the aqueous layer neutralized with 1.5N HC1 to pH 7 and extracted with ether (3 x 50 mL). The combined organic layer was washed with water (30 mL), brine (30 mL), dried (Na2S04), filtered, concentrated and the crude product was purified by silica gel chromatography (24 g Redisep® column, eluting with 30percent EtOAc in n-hexane) to afford the title compound (285 mg) as light brown solid. LC-MS Retention Time = 2.56 min; m/z = 285.2 [M+H]+. Column: KINETIX XB-C18, 75x3 mm, 2.6 muiotaeta; Flow rate: 1 mL/min; Mobile Phase A: 10 mM HCOONH4 in 98percent Water/ 2percent ACN; Mobile Phase B: 10 mM HCOONH4 in 2percent Water/ 98percent ACN; 20percent B to 100percent B over 4 min, then hold for 0.6 min at 100percent B with flow rate of 1.5 mL/min; Detection: UV at 220 nm. 1H NMR (400 MHZ, CDCl3) delta 8.90 (s, 1H), 7.70 (d, J=8 Hz, 1H), 7.36 -7.25 (m, 6H), 6.83 (dd, J=8.8, 2.0 Hz, 1H), 4.57 (s, 2H), 4.24 (br s, 1H), 3.76 (t, J=5.2 Hz, 2H), 3.42 (m, 2H).
  • 3
  • [ 42726-73-8 ]
  • [ 1462-37-9 ]
  • 1-tert-butyl 3-methyl 2-(2-benzyloxyethyl)malonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% General procedure: alpha-Monosubstituted malonic diester 1 was synthesized according to the reported procedure as follows.3 tert-Butyl methyl malonate was purchased from Kanto Chemical, and used without further purification. The physical properties and spectral data of the new compounds, 2-(2-methylbenzyl)malonate 1g, 2-prenylmalonate 1l, and 2-(2-benzyloxyethyl)malonate 1o, are listed below. A 100 mL round-bottom flask equipped with a stirring bar was charged with <strong>[42726-73-8]tert-butyl methyl malonate</strong> (846 muL, 5.0 mmol) and DMF (10 mL). To the solution, sodium hydride (60percent oil suspension, 200 mg, 5.0 mmol) was added. The reaction was allowed to stir at 0 °C for 30 min. To the mixture, corresponding alkyl halide (5.0 mmol) was added at 0 °C and the mixture was stirred at room temperature for 24 h. To the reaction mixture, H2O was added, and the mixture was extracted with CH2Cl2 (3 * 20 mL), dried over MgSO4, and concentrated in vacuo. The remaining residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford the desired product 1.
  • 4
  • [ 109-11-5 ]
  • [ 1462-37-9 ]
  • [ 892871-54-4 ]
YieldReaction ConditionsOperation in experiment
49% To a solution of <strong>[109-11-5]morpholin-3-one</strong> (cas: 109-11-5, 2 g, 19.8 mmol) in anhydrous DMF (25 mL) was added NaH (60% dispersion in mineral oil, 1.98 g, 2.5 equiv.) at 0 C under N2. The reaction mixture was stirred for 30 minutes and then ((2- bromoethoxy)methyl)benzene (cas: 1462-37-9, 1.98 g, 2.5 equiv.) was added to the reaction mixture, which was then allowed to warm to ambient temperature. After 12 hours, analysis by LC-MS indicated completion of the reaction. The reaction mixture was quenched with H20 (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic extracts were concentrated under reduced pressure to give the crude product, which was purified by silica gel chromatography (Petroleum ether: EtOAc = 1 :4) to provide morpholinone 1-339 as a pale oil (2.3 g, 49% yield). MS (ESI, pos. ion) m/z: 236(M+l).
  • 5
  • [ 126-33-0 ]
  • [ 1462-37-9 ]
  • 2-(2-(benzyloxy)ethyl)tetrahydrothiophene 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; at -78 - 20℃; A solution of I-16A (2.362 mL, 24.96 mmol) in THF (50 mL) was cooled to -78 C. To the chilled solution was added nBuLi (10.98 mL, 27.5 mmol) dropwise, followed by dropwise addition of benzyl-2-bromoethyl ether (3.99 mL, 25.2 mmol). The resulting solution was allowed to slowly warm to RT. Upon completion of the reaction, the mixture was cooled to 0 C. and quenched with H2O. The aqueous mixture was diluted with EtOAc. The phases were separated and the organic layer was washed with 2 M HCl and brine, dried over sodium sulfate, and concentrated under reduced pressure. The oily residue was purified by column chromatography (SiO2, 0-50% EtOAc/heptane) to afford I-16B as a colorless oil. LCMS m/z: 255 (M+1). 1H NMR (400 MHz, CDCl3) delta ppm 1.73-1.90 (m, 2H) 2.02-2.13 (m, 1H) 2.14-2.39 (m, 3H) 2.94-3.03 (m, 1H) 3.11-3.24 (m, 2H) 3.59-3.71 (m, 2H) 4.46-4.59 (m, 2H) 7.27-7.41 (m, 5H).
 

Historical Records

Technical Information

Categories

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[ 1462-37-9 ]

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(4-Hydroxyphenyl)(phenyl)methanone

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3-Chloropropiophenone

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