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Chemical Structure| 103724-99-8 Chemical Structure| 103724-99-8

Structure of 103724-99-8

Chemical Structure| 103724-99-8

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Product Details of [ 103724-99-8 ]

CAS No. :103724-99-8
Formula : C8H8BrCl
M.W : 219.51
SMILES Code : CC1=CC(Cl)=CC(C)=C1Br
MDL No. :MFCD07780649
InChI Key :CFMPIQSLDJXNPD-UHFFFAOYSA-N
Pubchem ID :5324738

Safety of [ 103724-99-8 ]

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

Computational Chemistry of [ 103724-99-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 49.08
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.65
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

4.73
Log Po/w (WLOGP)?

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

3.72
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.

4.25
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

4.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.88

Water Solubility

Log S (ESOL):?

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

-4.62
Solubility 0.00521 mg/ml ; 0.0000237 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.

-4.46
Solubility 0.00762 mg/ml ; 0.0000347 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

-4.65
Solubility 0.00495 mg/ml ; 0.0000225 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

Low
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

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

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.

-4.28 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

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

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)

1.42

Application In Synthesis of [ 103724-99-8 ]

* 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 [ 103724-99-8 ]

[ 103724-99-8 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 75-25-2 ]
  • [ 103724-96-5 ]
  • [ 103724-99-8 ]
  • 2
  • [ 103724-99-8 ]
  • [ 6045-90-5 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; N,N-dimethyl-formamide; B. 4-Chloro-2,6-dimethyl benzaldehyde Dissolve <strong>[103724-99-8]4-bromo-3,5-dimethyl chlorobenzene</strong> (6.5 g) in 50 mL anhydrous THF and cool to -78 C. (dry ice/acetone) under N2. Dropwise over 5 minutes add a solution of butyllithium (12.50 mL, 2.5M in hexanes) to the stirring solution of aryl bromide at -78 C. After 2 hours, dropwise add anhydrous DMF (5.0 mL) to the orange/red reaction solution and allow to warn to ambient temperature overnight while stirring under N2. Evaporate the yellow solution down to a yellow oil and partition between H2O (100 mL) and CH2Cl2 (100 mL). Extract the aqueous layer once with CH2Cl2, then pool the organic layers and dry over Na2SO4, filter and evaporate down to 5.0 g of yellow oil. Use without further purification. LCMS=169.6 (MH+)
With n-butyllithium; In tetrahydrofuran; N,N-dimethyl-formamide; B. 4-Chloro-2,6-dimethyl benzaldehyde Dissolve <strong>[103724-99-8]4-bromo-3,5-dimethyl chlorobenzene</strong> (6.5 g) in 50 mL anhydrous THF and cool to -78 C. (dry ice/acetone) under N2. Dropwise over 5 min add a solution of butyllithium (12.50 mL, 2.5M in hexanes) to the stirring solution of aryl bromide at -78 C. After 2 h, dropwise add anhydrous DMF (5.0 mL) to the orange/red reaction solution and allow to warn to ambient temperature overnight while stirring under N2. Evaporate the yellow solution down to a yellow oil and partition between H2O (100 mL) and CH2Cl2 (100 mL). Extract the aqueous layer once with CH2Cl2, then pool the organic layers and dry over Na2SO4, filter and evaporate down to 5.0 g of yellow oil. Use without further purification. LCMS=169.6 (MH+).
  • 3
  • 4-chloro-2,6-dimethylaniline hydrochloride [ No CAS ]
  • [ 103724-99-8 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; A. 4-Bromo-3,5-dimethyl chlorobenzene Slurry 2,6-dimethyl-4chloroaniline hydrochloride (23g, 193.11 g/mol) in CH2Cl2 (100 ml) and wash with saturated NaHCO3 to generate the free base. Dry over Na2SO4, filter and evaporate down to a violet oil. Slurry up in 120 mL 6.0 N H2SO4 and stir vigorously at ambient temperature to break up larger pieces of solid.
In dichloromethane; A. 4-Bromo-3,5-dimethyl chlorobenzene Slurry 2,6-dimethyl-4-chloroaniline hydrochloride (23 g, 193.11 g/mol) in CH2Cl2 (100 ml) and wash with saturated NaHCO3 to generate the free base. Dry over Na2SO4, filter and evaporate down to a violet oil. Slurry up in 120 mL 6.0 N H2SO4 and stir vigorously at ambient temperature to break up larger pieces of solid.
  • 4
  • [ 24596-18-7 ]
  • [ 103724-99-8 ]
YieldReaction ConditionsOperation in experiment
91% EXAMPLE 34-Chloro-2,6-dimethylbromobenzene; The procedure is as in Example 1, except that only 6.95 g [0.025 mol] of FeSO4×7H2O are used. This gives 20.7 g of an oil which, according to GC, contains 97.1% 4-chloro-2,6-dimethylbromobenzene (91% of theory).
  • 5
  • [ 19230-28-5 ]
  • [ 103724-99-8 ]
  • [ 1318253-20-1 ]
  • 6
  • [ 103724-99-8 ]
  • [ 1318253-21-2 ]
  • 7
  • [ 103724-99-8 ]
  • [2,6-bis(4-chloro-2,6-dimethylphenyl)phenyl]dimethylsilylium tetrakis(pentafluorophenyl)borate [ No CAS ]
  • 8
  • [ 103724-99-8 ]
  • [ 332179-32-5 ]
  • 9
  • [ 103724-99-8 ]
  • [ 1315482-74-6 ]
  • 10
  • [ 103724-99-8 ]
  • [ 68-12-2 ]
  • [ 6045-90-5 ]
  • 11
  • [ 626-05-1 ]
  • [ 103724-99-8 ]
  • [ 1610475-25-6 ]
  • 12
  • [ 103724-99-8 ]
  • [ 73183-34-3 ]
  • [ 1374578-82-1 ]
YieldReaction ConditionsOperation in experiment
31% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85℃; for 18h;Inert atmosphere; Sealed tube; In a microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed <strong>[103724-99-8]2-bromo-5-chloro-1,3-dimethylbenzene</strong> (250 mg, 1.14 mmol), pinacol diborane (347 mg, 1.37 mmol), KOAc (335 mg, 3.42 mmol), and the catalyst PdCl2(dppf) (83 mg, 0.11 mmol). Nitrogen gas was bubbled through a solution of dioxane (5.7 mL) and then the solution was added to the reaction mixture. The vial was capped and placed in an oil bath at 85 C for 18 h. The reaction mixture was and filtered on a pad of Celite and washed with dioxane.The solvent was evaporated under vacuum and the crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (1 to 2 % gradient) and afforded the title compound (94 mg, 0.35 mmol, 31%) as white solid.
31% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 20 - 85℃; for 18h;Inert atmosphere; Sealed tube; In a microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed <strong>[103724-99-8]2-bromo-5-chloro-1,3-dimethylbenzene</strong> (250 mg, 1.14 mmol), pinacol diborane (347 mg, 1.37 mmol), KOAc (335 mg, 3.42 mmol), and the catalyst Pd012(dppf) (83 mg, 0.11 mmol). Nitrogen gas was bubbled through a solution of dioxane (5.7 mL) and then the solution was added to the reaction mixture. The vial was capped and placed in an oil bath at 85 00 for 18 h. The reaction mixture was and filtered on a pad of Celite and washed with dioxane.The solvent was evaporated under vacuum and the crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (ito 2 % gradient) and afforded the title compound (94 mg, 0.35 mmol, 31%) as white solid.
  • 13
  • [ 103724-99-8 ]
  • 1-(4-(4-chloro-2,6-dimethylphenyl)-5-(isopropylthio)thiazol-2-yl)-4-(3-fluorophenyl)-3-methyl-1H-pyrazole-5-carboxylic acid [ No CAS ]
  • 14
  • [ 103724-99-8 ]
  • methyl 4-bromo-1-(4-(4-chloro-2,6-dimethylphenyl)-5-(isopropylthio)thiazol-2-yl)-3-methyl-1H-pyrazole-5-carboxylate [ No CAS ]
  • 15
  • [ 103724-99-8 ]
  • [ 75998-29-7 ]
  • (4-chloro-2,6-dimethylphenyl)(3-chloro-6-methoxybenzo[b]thiophen-2-yl)methanone [ No CAS ]
  • 16
  • [ 103724-99-8 ]
  • methyl (E)-3-(4-((2-(4-chloro-2,6-dimethylbenzoyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate [ No CAS ]
  • 17
  • [ 103724-99-8 ]
  • methyl (E)-3-(4-((2-(4-chloro-2,6-dimethylbenzoyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate [ No CAS ]
  • 18
  • [ 103724-99-8 ]
  • (E)-3-(4-((2-(4-chloro-2,6-dimethylbenzoyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid [ No CAS ]
  • 19
  • [ 103724-99-8 ]
  • [ 109-77-3 ]
  • 2-(4-chloro-2,6-dimethylphenyl)propanedinitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a 400 mL vessel equipped with a mechanical stirrer, thermometer, distillation head and dropping funnel, solid sodium hydroxide (10.9 g, 0.27 mol, microprills with 0.5 - 1 mm diameter) is charged under an inert atmosphere.1-Methyl-2-pyrrolidone (NMP, 137 g) is added to the vessel in one portion through the dropping funnel and the reaction mixture cooled to 10 - 15 C while stirring. A solution of malononitrile (NEC-CH2-CEN) (6.6 g, 0.10 mol) in NMP (8.9 g) is added through the dropping funnel over 10 - 15 minutes maintaining the temperature at 10 - 15 C. The reaction mixture is then heated to 100 C and a vacuum (30 mbar) applied, upon which solvent (40 g) is distilled off.2-Bromo-5-chloro-1 ,3-dimethyl-benzene (20 g, 0.089 mol) is then added through the dropping funnel over 5- 10 minutes, whilst maintaining the temperature at 100- 110 CC. A mixture containingpalladium (II) chloride (0.19 g, solution in conc. hydrochloric acid, assay 20% Pd, 0.36 mmol), triphenylphosphine (0.45 g, 1.6 mmol) and NMP (18 g) is then added through the dropping funnel over a 5 - 10 minute period. The temperature is allowed to rise to 124 C and the reaction mixture stirred at this temperature for 2 - 3 hours. Conversion is monitored by pulling samples and subsequent HPLC analysis.When conversion is complete, a vacuum (20-40 mbar) is applied and solvent (90 g) is distilled off. The resulting residue is cooled below 100 C and water (95 g) is added. After cooling to room temperature, the resulting mixture is filtered through hyflo (Hyflo SuperCel diatomaceous earth, ca. 10 g) and the filter cake washed with water (20 g). To the combined filtrates, hydrochloric acid (20.6 g, assay 32%, 0.18 mol) is added to adjust the pH from 13.3 to 2.7.The resulting mixture is extracted with tert-butyl-methyl ether (2 x 110 g). The organic phases are washed with water (2 x 50g) and the combined organic phases evaporated to dryness. The resulting solid residue is recrystallized from iso-propanol (63 g) and the resulting crystals filtered, washed with cold iso-propanol (5 g) and dried under vacuum to yield 2-(4-chloro-2,6-dimethyl-phenyl)propanedinitrile (melting point (m.p.) 145 - 147 C).
  • 20
  • [ 103724-99-8 ]
  • 2-(4-chloro-2,6-dimethylphenyl)acetic acid [ No CAS ]
  • 21
  • [ 75-21-8 ]
  • [ 103724-99-8 ]
  • 1-(4-chloro-2,6-dimethylphenyl)ethanol [ No CAS ]
  • 2-(4-chloro-2,6-dimethylphenyl)ethanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-50 C. from 10 mmol of <strong>[103724-99-8]4-chloro-2,6-dimethylbromobenzene</strong> and 11.1 mmol of magnesium in 10 ml of tetrahydrofuran, were metered in 8.8 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (22 mmol, calculated for a concentration of 2.5 M) at 50 C. over the course of 30 minutes. After 3 hours at 50 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was 87:13.
  • 22
  • [ 75-21-8 ]
  • [ 103724-99-8 ]
  • 2-(4-chloro-2,6-dimethylphenyl)ethanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-35 C. from 50 mmol of <strong>[103724-99-8]4-chloro-2,6-dimethylbromobenzene</strong>, 1 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium (to start the Grignard synthesis) and 55.5 mmol of magnesium in 50 ml of tetrahydrofuran, were added 5 mmol of copper(I) iodide. Then, 48 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (120 mmol, calculated for a concentration of 2.5 M) were metered in at 20 C. over the course of 30 minutes. After 16 hours at 20 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1. GC/MS: m/e=184 (M+ (35Cl), 25%), 153 (35Cl, 100%). 1H-NMR (600 MHz, d-DSMO): delta=2.28 (s, 6H), 2.75 (m, 2H), 3.45 (m, 2H), 4.74 (m, 1H), 7.0 (s, 2H) ppm.
  • 23
  • C13H11BBr2O [ No CAS ]
  • [ 103724-99-8 ]
  • C20H16BBr2Cl [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% Under an argon atmosphere, to a 200 ml three-neck flask, 96 ml of an anhydrous THF solution of 10.54 g (48.0 mmol) of <strong>[103724-99-8]2-bromo-5-chloro-1,3-dimethylbenzene</strong> was added and then, stirred at about -78 C. 30.0 ml (48.0 mmol) of a 1.6 M n-butyllithium hexane solution was added thereto dropwise, followed by stirring for about 1 hour. The solution thus obtained was added to a solution obtained by the first reaction dropwise, followed by heating and stirring at about 80 C. for about 2 hours for performing reaction. After cooling in the air, water was added, an organic layer was separately taken, and solvents were evaporated under a reduced pressure. The crude product thus obtained was separated by silica gel column chromatography to obtain 5.99 g (yield 27%) of Compound H as a white solid. The molecular weight of Compound H measured by FAB-MS was 459.
 

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Technical Information

Categories

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[ 103724-99-8 ]

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