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Structure of 1132832-75-7

Chemical Structure| 1132832-75-7

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Product Details of [ 1132832-75-7 ]

CAS No. :1132832-75-7
Formula : C18H12BrFOS
M.W : 375.25
SMILES Code : O=C(C1=CC(Br)=CC=C1C)C2=CC=C(C3=CC=C(F)C=C3)S2
MDL No. :MFCD25977368
InChI Key :DSNLQVKYUASMTN-UHFFFAOYSA-N
Pubchem ID :46930433

Safety of [ 1132832-75-7 ]

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

Computational Chemistry of [ 1132832-75-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 17
Fraction Csp3 0.06
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 92.25
TPSA ?

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

45.31 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.49
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

6.1
Log Po/w (WLOGP)?

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

6.28
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.

4.66
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

7.21
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.55

Water Solubility

Log S (ESOL):?

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

-6.38
Solubility 0.000155 mg/ml ; 0.000000414 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

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

-6.83
Solubility 0.0000552 mg/ml ; 0.000000147 mol/l
Class?

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

Poorly 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

-8.11
Solubility 0.00000291 mg/ml ; 0.0000000078 mol/l
Class?

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

Poorly 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

No
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

Yes
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

Yes
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.

-4.26 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

1.0
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

1.0
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

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)

2.93

Application In Synthesis of [ 1132832-75-7 ]

* 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 [ 1132832-75-7 ]

[ 1132832-75-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1132832-75-7 ]
  • [ 1030825-20-7 ]
YieldReaction ConditionsOperation in experiment
97.7% With borane-THF; In tetrahydrofuran; at -20 - -10℃; for 48h; 15 g (5-bromo-2-methylphenyl)[5-(p-fluorophe- nyl)thiophene-2-yl]methanone was weighed and dissolved in 150 ml tetrahydroffiran, and 30 ml of 1 M boranetetrahydroffiran complex was added. The system was reacted at ?20° C. to ?10° C. for 48 hours. After the complete reaction of raw materials, 30 ml water was added. The mixture was extracted with 100 ml dichloromethane, and then the extract was concentrated to give 14.25 g of 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene, with a purity of 98.9percent and in a yield of 97.7percent
84% With triethylsilane; boron trifluoride diethyl etherate; In dichloromethane; acetonitrile; at 0 - 35℃; 56.5 g of (5-bromo-2-methylphenyl)[2-(4-fluorophenyl)thiophene]methanone to be prepared according to Example 5. Dissolve (0.44 mol) in 600 ml of dichloromethane-acetonitrile (1:1, v/v), cool to 0°C in an ice water bath, and add dropwise triethylsilane.100 ml (0.63 mol), and then slowly added 47percent boron trifluoride ether 42 ml (0.33 mol), slowly added to the 20-The reaction was stirred at 35° C. for 4 hours. After the TLC reaction was completed, it was quenched with a saturated light carbonic acid solution and extracted with dichloromethane.The organic phase was washed with water and saturated brine, and the solvent was evaporated under reduced pressure. The residue was re-constituted with dichloromethane-methanol (1:1, v/v). Crystalline 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene, 13.3 g, yield 84percent
70% With triethylsilane; boron trifluoride diethyl etherate; In dichloromethane; acetonitrile; at 0 - 20℃; for 3h; Synthesis of compound 44Ci8Hi4BrFS M = 361.27 g.mol"1 19FNMR (CDCh, 282.5MHz): -115.0 (m, IF, Ar-F).Mass ESf): 133 (29percent); 177 (49percent); 182 (55percent); 184 (70percent); 191 (72percent); 281 (39percent); 360 (95percent); 362 (100percent)F Et3SiH DCM/MeCN Et3SiH (0.99mL, 6.18mmol, 2.9eq) was added at room temperature to a solution of ketone 43 (800mg, 2.13mmol, leq) in anhydrous dichloromethane-acetonitrile (1 :1, v/v, 16mL). The resultant mixture was cooled to 0°C and BF3.Et20 (0.75mL, 5.97mmol, 2.8eq) was slowly added. The reaction mixture was then stirred at room temperature for 3 hours. A saturated aqueous solution of NaHC03 was slowly added at 0°C. The aqueous layer was extracted with dichloromethane and the resultant organic layer was dried over MgS04, filtered and concentrated. The crude mixture was then recristallized with MeOH to afford compound 44 (70percent yield) as yellowish crystals.
With triethylsilane; boron trifluoride diethyl etherate; In dichloromethane; acetonitrile; at -8 - 20℃; Example 2; 2-(5-Bromo-2-methyl-benzyl)-5-(4-fluoro-phenyl)-thiopheneA 3.0 L four-necked round bottom flask was charged with the compound prepared as in Example 1 above (119 g, 0.317 mol), triethylsilane (148 ml_,0.926 mol), dichloromethane (700 ml_) and acetonitrile (700 ml_). The resulting mixture was cooled to -80C in an ice bath, with stirring, then boron thfluohde diethyl etherate (115 ml_, 0.915 mol) was added dropwise, such that the temperature did not exceed O0C. The resulting mixture was warmed to room <n="79"/>temperature and stirred overnight. The resulting mixture was concentrated under reduced pressure, diluted with IPA (1.0 L), filtered and washed with water to yield a solid. Recrystallization of the solid from IPA yielded the title compound as a yellow solid.
3.65 g With triethylsilane; boron trifluoride diethyl etherate; In dichloromethane; acetonitrile; at 0 - 20℃; for 26h; 2-(5-Bromo-2-methyl-benzoyl)-5-(4-fluoro-phenyl)-phenyl)-thiophene (8, 3.75 g) was dissolved in dichloromethane (40 ml) and acetonitrile (40 ml), to which triethylsilane (4.63 ml) was added and cooled to 0 °C. Boron trifluoride etherate (3.45 ml) was added to the suspension and the reaction mixture was left to warm up to room temperature then continued to stir at that temperature for 26 h. The reaction mixture was cooled on ice and 50 ml of NaHCO3 was slowly added, followed by adding dichloromethane (50 ml). Phases were separated and organic phase was dried over sulphate, and then evaporated. The residue was recrystallized from 2-propanol to give 3.65 g of the title compound 1a. 13C NMR (DMSO): 18.52, 32.84, 115.83, 116.00, 118.81, 123.52, 126.86, 126.99, 127.05, 129.50, 130.41, 131.60, 132.37, 135.54, 140.63, 141.16, 142.46, 160.48, 162.42. MS, m/z= 360.
With aluminum (III) chloride; sodium tetrahydroborate; In 1,2-dimethoxyethane; at 0 - 70℃; Aluminum chloride (46.12 g) was added to 1,2-dimethoxyethane (260 mL) at 0°C to 5°C. The reaction mixture was stirred for 30 minutes to 40 minutes at 5°C to 10°C. Sodium borohydride (26.19 g) was slowly added to the reaction mixture at 5°C to 10°C. The reaction mixture was stirred for 25 minutes to 30 minutes at the same temperature. A solution of (5-bromo-2-methylphenyl)[5-(4-fluorophenyl)thiophen-2-yl]methanone (130 g; Example 2) in 1,2-dimethoxyethane (260 mL) was added slowly to the reaction mixture, and then the mixture was stirred for 60 minutes at 15°C to 20°C. The reaction mixture was heated to a temperature of 65 °C to 70°C, and then stirred for 5 hours to 6 hours at the same temperature. After completion of the reaction, the reaction mixture was cooled to a temperature of 0°C to 5°C, and then added to pre-cooled de-ionized water (1300 mL) at 0°C to 10°C. The reaction mixture was stirred for 10 minutes to 15 minutes at the same temperature. Ethyl acetate (1300 mL) was added to the reaction mixture, and then the mixture was stirred for 10 to 15 minutes at 25°C to 30°C. The reaction mixture was allowed to settle for 15 minutes and then the layers were separated. The aqueous layer was washed with ethyl acetate (260 mL) and the organic layer was separated. The organic layers were combined, and then washed with an aqueous solution of sodium bicarbonate (32.5 g of sodium bicarbonate in 650 mL of de-ionized water). The organic layer was then washed with de-ionized water (260 mL). The organic layer was concentrated under reduced pressure at a temperature of about 45°C to obtain a solid residue. Methanol (390 mL) was added to the solid residue, and then the mixture was stirred for 60 minutes to 120 minutes at 0°C to 5°C to obtain a solid. The solid was washed with methanol (130 mL), and then dried under reduced pressure at 40°C to 45 °C to obtain 2-(5-bromo-2- methylbenzyl)-5 -(4-fluorophenyl)thiophene . Yield: 93percent

 

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Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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