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Chemical Structure| 57381-62-1 Chemical Structure| 57381-62-1

Structure of 57381-62-1

Chemical Structure| 57381-62-1

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Product Details of [ 57381-62-1 ]

CAS No. :57381-62-1
Formula : C8H6BrClO2
M.W : 249.49
SMILES Code : O=C(OC)C1=CC=C(Cl)C=C1Br
MDL No. :MFCD10566822
InChI Key :BIFARHLBYAKSSN-UHFFFAOYSA-N
Pubchem ID :15110995

Safety of [ 57381-62-1 ]

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

Computational Chemistry of [ 57381-62-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 50.43
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.

2.46
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

4.12
Log Po/w (WLOGP)?

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

2.89
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.

3.24
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

3.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.14

Water Solubility

Log S (ESOL):?

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

-4.22
Solubility 0.015 mg/ml ; 0.0000602 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.38
Solubility 0.0104 mg/ml ; 0.0000418 mol/l
Class?

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

Moderately 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

-3.95
Solubility 0.0282 mg/ml ; 0.000113 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.

-4.9 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)

1.59

Application In Synthesis of [ 57381-62-1 ]

* 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 [ 57381-62-1 ]

[ 57381-62-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 292638-84-7 ]
  • [ 57381-62-1 ]
  • 4-Chloro-2-((E)-styryl)-benzoic acid methyl ester [ No CAS ]
  • 2
  • [ 74-85-1 ]
  • [ 57381-62-1 ]
  • [ 131001-87-1 ]
  • 3
  • C18H29BFNO3S [ No CAS ]
  • [ 57381-62-1 ]
  • [ 943975-38-0 ]
  • 5
  • [ 57381-62-1 ]
  • C22H19ClF4N2O4 [ No CAS ]
  • 6
  • [ 57381-62-1 ]
  • 4-chloro-2-styrylbenzamide [ No CAS ]
  • 7
  • [ 57381-62-1 ]
  • 4-chloro-2-styrylbenzoic acid [ No CAS ]
  • 8
  • [ 57381-62-1 ]
  • 4-Chloro-2-((E)-styryl)-benzoyl chloride [ No CAS ]
  • 9
  • [ 57381-62-1 ]
  • 6-chloro-3-phenyl-1H-isochromen-1-one [ No CAS ]
  • 10
  • [ 57381-62-1 ]
  • 6-chloro-3-phenylisoquinolin-1(2H)-one [ No CAS ]
  • 11
  • [ 57381-62-1 ]
  • 1-keto-6-chloro-3-phenyl-4-(phenylseleno)-1,2,3,4-tetrahydroisoquinoline [ No CAS ]
  • 12
  • [ 57381-62-1 ]
  • [ 131001-97-3 ]
  • 13
  • [ 57381-62-1 ]
  • [ 131001-93-9 ]
  • 14
  • [ 765-43-5 ]
  • [ 57381-62-1 ]
  • [ 170106-70-4 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; REFERENCE EXAMPLE 3 Cyclopropylmethylketone (4.0 g) was added to a suspension of sodium hydride (3.2 g, 60percent oil dispersion) in dry tetrahydrofuran (10 ml). When the evolution of hydrogen had subsided, a solution of <strong>[57381-62-1]methyl 2-bromo-4-chlorobenzoate</strong> (10.0 g) in tetrahydrofuran was added dropwise. The resulting mixture was heated at reflux overnight, cooled, evaporated to dryness and poured onto dilute hydrochloric acid. The mixture was extracted (dichloromethane), dried (magnesium sulphate) and evaporated to give, after purification by chromatography, 1-(2-bromo-4-chlorophenyl)-3-cyclopropyl-propan-1,3-dione (3.07 g), m.p. 42°-45° C. as an orange solid.
  • 15
  • [ 57381-62-1 ]
  • [ 81290-20-2 ]
  • [ 1033805-24-1 ]
YieldReaction ConditionsOperation in experiment
51% With tetrabutyl ammonium fluoride; In toluene; at -70 - 20℃; for 14h; <strong>[57381-62-1]2-bromo-4-chloro-benzoic acid methyl ester</strong> (12.4 g, 50 mmol) in toluene (200 ml) was cooled to -70 ° C and trifluoroMethyltrimethylsilane (13 ml, 70 mmol). Tetrabutylammonium fluoride (IM, 2.5 ml) was added dropwise and the mixture was allowed to stand for 4 hoursHeated to room temperature, followed by stirring at room temperature for 10 hours. The reaction mixture was concentrated to give crude [l- (2-bromo-4-chloro-phenyl) -2,2,2-trifluoro-1-methoxy-ethoxy] -trimethyl-silane. The crude intermediate was dissolved in methanol (100 ml) and added6N HCl (100 ml). The mixture was maintained at 45-50 & lt; 0 & gt; C for 12 hours. The methanol was removed and the crude product was extracted with dichloromethane (200 ml)Extract. The combined DCM layers were washed with water (50 ml), NaHCO3 (50 ml), brine (50 ml) and dried over sodium sulfate. Removal of dissolvedThe crude product was purified by ISCO column chromatography using 1-2percent ethyl acetate in hexanes as solventTo give 1- (2-bromo-4-chloro-phenyl) -2,2,2-trifluoro-ethanone (10 g, 70percent).
With tetrabutyl ammonium fluoride; In toluene; at -70 - 20℃; for 14h; 2-Bromo-4-chloro-benzoic acid methyl ester (12.4 g, 50 mmol) in toluene (200 ml) was cooled to -70° C., and trifluoromethyl trimethyl silane (13 ml, 70 mmol) was added. Tetrabutylammonium fluoride (1M, 2.5 ml) was added dropwise, and the mixture was allowed to warm to room temperature over 4 h, after which it was stirred for 10 h at room temperature. The reaction mixture was concentrated to give the crude [1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-1-methoxy-ethoxy]-trimethyl-silane.
In toluene; 2-Bromo-4-chloro-benzoic acid methyl ester (12.4 g, 50 mmol) in toluene (200 ml) was cooled to -70° C., and trifluoromethyl trimethyl silane (13 ml, 70 mmol) was added. Tetrabutylamonium fluoride (1M, 2.5 ml) was added dropwise, and the mixture was allowed to warm to room temperature over 4 h, after which it was stirred for 10 h at room temperature. The reaction mixture was concentrated to give the crude [1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-1-methoxy-ethoxy]-trimethyl-silane.
  • 16
  • [ 67-56-1 ]
  • [ 936-08-3 ]
  • [ 57381-62-1 ]
YieldReaction ConditionsOperation in experiment
99% Step 1: Synthesis of 1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-ethanone. To a 500 ml 2 necked RB flask containing anhydrous methanol (300 ml) was added thionyl chloride (29.2 ml, 400 mmol) dropwise at 0-5 C. (ice water bath) over 10 min. The ice water bath was removed, and 2-bromo-4-chloro-benzoic acid (25 g, 106 mmol) was added. The mixture was heated to mild reflux for 12 h. Progress of the reaction was monitored by TLC and LCMS. After completion of the reaction, the reaction mixture was concentrated. Crude product was dissolved in dichloromethane (DCM, 250 ml), washed with water (50 ml), sat. aq. NaHCO3 (50 ml), brine (50 ml), dried over sodium sulfate, and concentrated to give the 2-bromo-4-chloro-benzoic acid methyl ester (26 g, 99%), which was directly used in the following step.
99% With thionyl chloride; at 0℃;Reflux; Thionyl chloride (29.2 ml, 400 mmol) was added dropwise over 10 minutes at 0-5 C (ice-water bath) in a 500 ml 2-necked RB flask containing anhydrous methanol (300 ml).Remove the ice-water bath and add 2-bromo-4-chloro-benzoic acid (25 g, 106 mmol).The mixture was heated to moderate reflux for 12 hours.Reaction progress was monitored by TLC and LCMS. After completion of the reaction, the reaction mixture was concentrated.The crude product was dissolved in dichloromethane (DCM, 250 ml)Washed with water (50 ml), saturated aqueous NaHCO3 (50 ml), brine (50 ml)Dried over sodium sulfate,Concentration gave 2-bromo-4-chloro-benzoic acid methyl ester (26 g, 99%) which was used directly in the next step.
98% With sulfuric acid;Cooling with ice; Heating; Reflux; Concentrated sulfuric acid (5 ml_) was added drop-wise to an ice-cold mixture of 2- bromo-4-chloro-benzoic acid (10.14 g, 0.0431 mol) and methanol (40 ml_). The resulting mixture was heated at reflux for 17 hours. After this time, the reaction mixture was cooled to room temperature, and then poured into ice-cold water (150 ml_), creating a white suspension. The suspension was extracted with ethyl acetate (150 ml_). The organic phase was washed with saturated aqueous NaHCO3 (I OO ml_), followed by saturated aqueous NaCI (100 ml_). The organic layer was dried over Na2SO4, filtered, and concentrated to afford 2-bromo-4-chloro-benzoic acid methyl ester (10.57 g, 98% yield) as a clear oil.
  • 17
  • [ 936-08-3 ]
  • [ 57381-62-1 ]
YieldReaction ConditionsOperation in experiment
99% With thionyl chloride; In methanol; dichloromethane; Step 1: Synthesis of 1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-ethanone. To a 500 ml 2 necked RB flask containing anhydrous methanol (300 ml) was added thionyl chloride (29.2 ml, 400 mmol) dropwise at 0-5° C. (ice water bath) over 10 min. The ice water bath was removed, and 2-bromo-4-chloro-benzoic acid (25 g, 106 mmol) was added. The mixture was heated to mild reflux for 12 h. Progress of the reaction was monitored by TLC and LCMS. After completion of the reaction, the reaction mixture was concentrated. Crude product was dissolved in dichloromethane (DCM, 250 ml), washed with water (50 ml), sat. aq. NaHCO3 (50 ml), brine (50 ml), dried over sodium sulfate, and concentrated to give the 2-bromo-4-chloro-benzoic acid methyl ester (26 g, 99percent), which was directly used in the following step.
  • 18
  • [ 57381-62-1 ]
  • [ 143888-84-0 ]
YieldReaction ConditionsOperation in experiment
A 1.0 M solution of diisobutylaluminum hydride in toluene (43 ml_, 0.043 mol) was added slowly drop-wise to a -78 °C solution of <strong>[57381-62-1]2-bromo-4-chloro-benzoic acid methyl ester</strong> (10.57 g, 0.042 mol) in toluene (50 ml_) and hexanes (425 ml_). The reaction mixture was stirred at -78 °C for 1.5 hours. After this time, a white solid had precipitated out of solution. The reaction mixture was quenched at -78 °C with ethyl acetate (100 ml_). Saturated aqueous sodium potassium tartrate was added, and the reaction mixture was warmed to room temperature. The organic phase was separated, dried over Na2SO4, filtered, and concentrated to a clear oil. TLC (30percent ethyl acetate/hexanes) and 1H NMR revealed a mixture with unreacted 2-bromo-4- chloro-benzoic acid methyl ester as the major component. The crude material was dissolved in toluene (300 ml_), and the resulting solution was cooled to -78 °C. A 1.0 M solution of diisobutylaluminum hydride in toluene (55 ml_, 0.055 mol) was added slowly drop-wise to the reaction mixture. The reaction mixture was warmed to - 45 °C and stirred at this temperature for 35 minutes. At this time, TLC (10percent ethyl acetate/hexanes) indicated nearly complete consumption of the starting material. The reaction mixture was quenched at -45 °C with ethyl acetate. Saturated aqueous sodium potassium tartrate was added, and the reaction mixture was warmed to room temperature and stirred at room temperature for 1 hour. The organic phase was separated, dried over Na2SO4, and concentrated to a yellow oil. A solution of this crude product and dichloromethane (200 mL) was evaporated onto silica gel, and the dry silica gel-supported product was loaded onto a 120 g silica gel column. Flash chromatography was carried out using an ISCO purification system (95:5 hexanes- ethyl acetate ramped to 4:1 hexanes-ethyl acetate). (2-Bromo-4-chloro-phenyl)- methanol was isolated as 5.57 g (60percent yield) of a white solid.
  • 19
  • [ 89466-08-0 ]
  • [ 57381-62-1 ]
  • 9-chloro-6H-benzo[c]chromen-6-one [ No CAS ]
  • 20
  • [ 936-08-3 ]
  • [ 77-78-1 ]
  • [ 57381-62-1 ]
  • 21
  • [ 97674-02-7 ]
  • [ 57381-62-1 ]
  • C12H13ClO3 [ No CAS ]
  • 22
  • [ 57381-62-1 ]
  • C10H9ClO3 [ No CAS ]
  • 23
  • [ 57381-62-1 ]
  • C17H13ClN2O3 [ No CAS ]
  • 24
  • [ 57381-62-1 ]
  • C16H11ClN2O3 [ No CAS ]
  • 25
  • [ 57381-62-1 ]
  • [ 1338223-97-4 ]
  • 26
  • [ 135-67-1 ]
  • [ 57381-62-1 ]
  • [ 1380170-32-0 ]
YieldReaction ConditionsOperation in experiment
83% With potassium carbonate; sodium sulfate;copper; In nitrobenzene; at 220℃; for 7h;Inert atmosphere; The following reagents and solvent were loaded into a reactor.10H-Phenoxazine: 10.0 g (54.58 mmol)Methyl 2-bromo-4-chlorobenzoate : 15.12 g (60.65 mmol) Copper: 3.85 g (60.65 mmol)Potassium carbonate: 8.38 g (60.65 mmol)Sodium sulfate: 8.61 g (60.65 mmol)Nitrobenzene: 125 ml [0110] Next, the reaction solution was stirred with heating under nitrogen at 220°C for 7 hours. After the completion of the reaction, the reaction solution was concentrated under reduced pressure. To the resultant residue was added ethyl acetate, and the mixture was then washed with an aqueous solution of ammonium chloride. The organic layer was concentrated under reduced pressure to give a crude product. Next, the resultant crude product was purified by columnchromatography (silica gel) to afford 15.9 g of methyl 5-chloro-2- ( lOH-phenoxazin-10-yl ) benzoate (yield: 83percent)
  • 27
  • [ 57381-62-1 ]
  • [ 1380170-33-1 ]
  • 28
  • [ 57381-62-1 ]
  • [ 1380170-34-2 ]
  • 29
  • [ 57381-62-1 ]
  • [ 1380170-35-3 ]
  • 30
  • [ 57381-62-1 ]
  • [ 1380170-31-9 ]
  • 32
  • [ 57381-62-1 ]
  • [ 1541201-76-6 ]
  • 33
  • [ 57381-62-1 ]
  • [ 1541201-78-8 ]
  • 34
  • [ 57381-62-1 ]
  • C19H18ClN3O3 [ No CAS ]
  • 35
  • [ 57381-62-1 ]
  • C18H16ClN3O [ No CAS ]
 

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Technical Information

Categories

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[ 57381-62-1 ]

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