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Chemical Structure| 17715-69-4 Chemical Structure| 17715-69-4

Structure of 1-Bromo-2,4-dimethoxybenzene
CAS No.: 17715-69-4

Chemical Structure| 17715-69-4

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Product Details of [ 17715-69-4 ]

CAS No. :17715-69-4
Formula : C8H9BrO2
M.W : 217.06
SMILES Code : COC1=CC=C(Br)C(OC)=C1
MDL No. :MFCD00009844
InChI Key :NIUZVSQOXJIHBL-UHFFFAOYSA-N
Pubchem ID :87266

Safety of [ 17715-69-4 ]

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

Computational Chemistry of [ 17715-69-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.13
TPSA ?

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

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.5
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

2.57
Log Po/w (WLOGP)?

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

2.47
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.

2.22
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

2.49
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.45

Water Solubility

Log S (ESOL):?

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

-3.08
Solubility 0.182 mg/ml ; 0.000838 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.

-2.61
Solubility 0.538 mg/ml ; 0.00248 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

-3.51
Solubility 0.0668 mg/ml ; 0.000308 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.

-5.8 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

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<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)

1.64

Application In Synthesis of [ 17715-69-4 ]

* 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 [ 17715-69-4 ]

[ 17715-69-4 ] Synthesis Path-Downstream   1~14

  • 2
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  • [ 16932-45-9 ]
  • [ 20469-65-2 ]
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  • [ 185342-88-5 ]
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  • [ 76041-86-6 ]
  • [ 213479-73-3 ]
  • 5
  • [ 17715-69-4 ]
  • [ 133730-34-4 ]
YieldReaction ConditionsOperation in experiment
610.2 mg With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; hexane; at -78 - 20℃; for 2.66667h;Inert atmosphere; 576 μl of 1-bromo-2,4-dimethoxybenzene was dissolved in 5.8 ml of tetrahydrofuran and 3 ml of a 1.6 mol/l solution of n-butyllithium in hexane was added dropwise under an argon atmosphere at -78 C. Then, 1.1 ml of triisopropyl borate was added, followed by stirring at -78 C. for 40 minutes and then stirring at room temperature for 2 hours. To the reaction mixture were added 40 ml of water and 1 ml of 5N-hydrochloric acid, followed by extracting with 50 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, subsequently the solvent was distilled off under reduced pressure, and purification using silica gel column chromatography (hexane:ethyl acetate=2:1) afforded 610.2 mg of the title compound. [0296] 1H-NMR (CDCl3); δ (ppm) 3.85 (3H, s), 3.89 (3H, s), 5.81 (2H, s), 6.46 (1H, s), 6.56 (1H, dd, J=2.0, 8.4 Hz), 7.77 (1H, d, J=8.4 Hz).
610.2 mg With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; hexane; at -78 - 20℃; for 2.66667h;Inert atmosphere; 576 μl of 1-bromo-2,4-dimethoxybenzene was dissolved in 5.8 ml of tetrahydrofuran and 3 ml of a 1.6 mol/l solution of n-butyllithium in hexane was added dropwise under an argon atmosphere at -78C. Then, 1.1 ml of triisopropyl borate was added, followed by stirring at -78C for 40 minutes and then stirring at room temperature for 2 hours. To the reaction mixture were added 40 ml of water and 1 ml of 5N-hydrochloric acid, followed by extracting with 50 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, subsequently the solvent was distilled off under reduced pressure, and purification using silica gel column chromatography (hexane:ethyl acetate=2:1) afforded 610.2 mg of the title compound. 1H-NMR (CDCl3); δ (ppm) 3.85 (3H, s), 3.89 (3H, s), 5.81 (2H, s), 6.46 (1H, s), 6.56 (1H, dd, J=2.0, 8.4Hz), 7.77 (1H, d, J=8.4Hz).
  • 6
  • [ 17715-69-4 ]
  • [ 459-04-1 ]
  • [ 872990-99-3 ]
YieldReaction ConditionsOperation in experiment
30% With aluminum (III) chloride; In dichloromethane; at 3 - 8℃; for 0.416667h; Example 47: l-(5-Benzo[6]thien-2-yl-2,4-dimethoxy-phenyl)-2-(4-fluoro-phenyl)- propenone[0420] Ex-47A: l-Bromo-2,4-dimethoxybenzene (1.58 g, 7.27 mmol), 4-fluorophenyl acetyl chloride (1.00 mL, 7.42 mmol) and CH2Cl2 (20 mL) were sequentially charged into a clean reaction vessel and the resulting solution was cooled to 3 0C. AlCl3 (2.0 g, 15.0 mmol) was then added over 20 min and aged at 8 0C. After an additional 5 min, the reaction was poured into 75 mL cold H2O and extracted with EtOAc. The organic cut was washed with saturated NaHCO3, dried with MgSO4, filtered and concentracted to dryness. The crude product was dissolved in EtOAc and crystallized upon hexane addition. The product was filtered and then further purified by silica gel chromatography (20% EtOAc in hexanes) to afford 0.78 g (30% yield) of desired l-(5-bromo-2,4- dimethoxy-phenyl)-2-(4-fluoro-phenyl)-ethanone. 1H-NMR (CDCl3) δ 8.00 (s, IH), 7.13-7.18 (m, 2H), 6.95-7.01 (m, 2H), 6.44 (s, IH), 4.22 (s, 2H), 3.95 (s, 3H), 3.94 (s, 3H).
  • 7
  • [ 17715-69-4 ]
  • [ 133730-34-4 ]
  • [ 3153-72-8 ]
  • 8
  • [ 17715-69-4 ]
  • [ 3153-72-8 ]
  • [ 151-10-0 ]
  • 9
  • [ 17715-69-4 ]
  • [ 570-02-5 ]
  • [ 80202-76-2 ]
YieldReaction ConditionsOperation in experiment
Add (4.23 g, 19.47 mmol) 1-bromo-2,4-dimethoxybenzene (CAS 17715-69-4) to an appropriately sized round bottom flask. Attach a rubber septum to seal the flask. Insert a needle into the septum as a vent and flush the round bottom flask with nitrogen for about 10 minutes. Add (80 mL) anhydrous ether (CAS 60-29-7), followed by the drop wise addition of n-butyllithium (CAS 109-72-8) in hexane (CAS 110-54-3) (1.6M, 12.2 mL). Stir the cloudy mixture for 10 minutes and keep the round bottom flask on ice. Dissolve (2.20 g, 9.74 mmol) of methyl 2,4,6-trimethoxybenzoate (CAS 29723-28-2) in about 20 ml of anhydrous ether (CAS 60-29-7) (more than 20 mL can be used if needed), and then add this drop wise to the reaction mixture. (0163) After the addition is complete, stir the reaction mixture for about 3 minutes longer. Pour the reaction mixture into a separatory funnel containing 5% NH4Cl (aq) (CAS 12125-02-9) (50 mL) and shake until a color change is observed (pale orange). The layers are allowed to separated, and dry the top ether layer with about 5 g anhydrous Na2SO4 (CAS 7757-82-6), filter, and rotovapped to dryness at 35-40 C. under 400 mbar. Place the crude oil of heptamethoxy red (yellow-orange in color) into the freezer. Yield is 3.1 g.
  • 12
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  • [ 4038-15-7 ]
  • 13
  • [ 17715-69-4 ]
  • [ 3282-99-3 ]
  • C50H54N2O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
74.9% With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 100 - 108℃; for 8h;Inert atmosphere; The reaction route is as follows:A 250 mL three-necked flask was charged with 2.66 g (0.01 mol) of 1,1-bis (4-aminophenyl) cyclohexane, 9.75 g(0.045 mol) of 2,4-dimethoxybromobenzene, 5.60 g (0.05 mol) of potassium t-butoxide and 53.2 g of toluene. Nitrogen protection added0.366 g (4.0 × 10 -4 mol) of Pd 2 (dba) 3,0.232 g (8.0 × 10 -4 mol) (t-Bu) 3PH · BF 4,The temperature was raised to 100 C to 108 C and refluxed for 8 hours.Completed the reaction,The reaction solution was filtered,20g toluene leaching cake,The filtrate through a silica gel column,Decompression solvent was reddish brown viscous liquid.The above crude product was treated with THF,Toluene (mass ratio of 3: 3) recrystallization,6.1g white solid was obtained,Yield: 74.9%.
  • 14
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  • [ 55124-35-1 ]
  • [ 17715-69-4 ]
  • [ 133730-34-4 ]
YieldReaction ConditionsOperation in experiment
70% General procedure: To a solution in THF (4 mL) of DIPAB (863 mg, 7.5 mmol) and Mg (182 mg, 7.5 mmol) were added a PhMgBr 1M THF solution (375 μL, 375μmol) at room temperature. After 10 min, 30 mL of anhydrous THF were added followed by the arylbromide (5 mmol). The reaction mixture was cooled down to 0 C and quenched slowly with 7 mL of MeOH. After 1h, volatile were removed under reduced pressure and the resulting solid was dissolved in 1N HCl/MeOH (7/3). After 1h at room temperature, 100 mL of AcOEt were added, the organic phase was washed with 1N HCl (30 mL) and brine (3×30 mL). Organic phases were concentrated under reduced pressure yielding a solid which was recrystallized from H2O.
 

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