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Structure of 139911-28-7

Chemical Structure| 139911-28-7

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Product Details of [ 139911-28-7 ]

CAS No. :139911-28-7
Formula : C9H8BrFO2
M.W : 247.06
SMILES Code : CCOC(=O)C1=C(Br)C=CC(F)=C1
MDL No. :MFCD06204688
InChI Key :ODFAIHQRCRQZGM-UHFFFAOYSA-N
Pubchem ID :15037299

Safety of [ 139911-28-7 ]

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

Computational Chemistry of [ 139911-28-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 50.19
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.

2.2
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

2.93
Log Po/w (WLOGP)?

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

3.19
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.

3.38
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

3.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.97

Water Solubility

Log S (ESOL):?

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

-3.36
Solubility 0.108 mg/ml ; 0.000435 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.

-3.14
Solubility 0.177 mg/ml ; 0.000718 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

-4.02
Solubility 0.0238 mg/ml ; 0.0000964 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

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.

-5.73 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)

1.82

Application In Synthesis of [ 139911-28-7 ]

* 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 [ 139911-28-7 ]

[ 139911-28-7 ] Synthesis Path-Downstream   1~19

  • 2
  • [ 139911-28-7 ]
  • [ 144-55-8 ]
  • [ 497-19-8 ]
  • [ 139911-29-8 ]
  • ethyl 2-(2-methyl-4-fluorophenyl)-5-fluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.4 g (92%) tetrakis(triphenylphosphine)palladium (0); In ethanol; toluene; Ethyl 2-(2-Methyl-4-fluorophenyl)-5-fluorobenzoate Tetrakis(triphenylphosphine)palladium(0) (0.02 eq, 0.31 g) was added to a vigorously stirred solution of <strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (1.0 eq, 3.3 g, 0.013 mol) and 2-methyl-4-fluorophenylboronic acid (1.2 eq, 0.016 mol, 2.4 g) in 45 mL of toluene, 22 mL of 2M aqueous sodium carbonate, and 11 mL of ethanol and the mixture was refluxed for 9 h. The cooled reaction mixture was poured into 50 mL each of water, ammonium hydroxide, and 2M aqueous sodium bicarbonate and then filtered through Celite. The filtrate was extracted with ethyl acetate and the organics were dried (MgSO4) and concentrated to yield 3.9 g of a yellow oil. Chromatography (silica gel, 20% ethyl acetate/hexane) gave 3.4 g (92%) of product as a light colored oil. 1 H NMR (CDCl3, 60 mHz) delta 7.7 (dd, 1 H), 7.5 (m, 1 H), 7.25- 6.75 (m, 4 H), 4.0 (q, 2 H), 2.0 (s, 3 H), 1.0 (t, 3 H); IR (CDCl3 solution) 3130, 2220, 1700, 1450, 1080 cm-1; MS m/z 276 (M+), 201 (base peak).
  • 3
  • [ 14221-01-3 ]
  • [ 139911-28-7 ]
  • [ 144-55-8 ]
  • [ 497-19-8 ]
  • [ 139911-29-8 ]
  • ethyl 2-(2-methyl-4-fluorophenyl)-5-fluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.4 g (92%) In ethanol; toluene; Ethyl 2-(2-Methyl-4-fluorophenyl)-5-fluorobenzoate Tetrakis(triphenylphosphine)palladium(O) (0.02 eq, 0.31 g) was added to a vigorously stirred solution of <strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (1.0 eq, 3.3 g, 0.013 mol) and 2-methyl-4-fluorophenylboronic acid (1.2 eq, 0.016 mol, 2.4 g) in 45 mL of toluene, 22 mL of 2M aqueous sodium carbonate, and 11 mL of ethanol and the mixture was refluxed for 9 h. The cooled reaction mixture was poured into 50 mLeach of water, ammonium hydroxide, and 2M aqueous sodium bicarbonate and then filtered through Celite. The filtrate was extracted with ethyl acetate an the organics were dried (MgSO4) and concentrated to yield 3.9 g of a yellow oil. Chromatography (silica gel, 20% ethyl acetate/hexane) gave 3.4 g (92%) of product as a light colored oil. 1 H NMR (CDCl3, 60 mHz) delta7.7 (dd, 1H), 7.5 (m, 1H), 7.25-6.75 (m, 4H), 4.0 (q, 2H), 2.0 (s, 3H), 1.0 (t, 3H); IR (CDCl3 solution) 3130, 2220, 1700, 1450, 1080 cm-1; MS m/z 276 (M+), 201 (base peak).
  • 5
  • [ 557-21-1 ]
  • [ 139911-28-7 ]
  • ethyl 2-cyano-5-fluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; In N,N-dimethyl-formamide; at 130.0℃; for 4.0h;Inert atmosphere; Example 2 - ethyl 2-cyano-5-fluorobenzoateZinc cyanide (26.5 g; 0.225 mol) and Pd2(dba)3 (1.9 g; 3.4 mmol) were added to a solution of <strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (27.9 g; 0.112 mol) in DMF (71 ml).Triphenyl phosphine (2.9 g; 11 mmol) was added and then the reaction mixture was stirred at 130C under nitrogen atmosphere for 4 hours. The mixture was poured out into H20 (300 ml) and then extracted with EtOAc (200 ml). The organic layer was separated, washed with H20 (2 x 100 ml), brine (100 ml), dried (MgSC^), filtered and the solvent was evaporated.The residue was purified by column chromatography over silica gel (eluent: hexanes/ EtOAc (5/1, v/v)). The product fractions were collected and the solvent was evaporated.Yield: 20 g (93%; orange solid).
93% With triphenylphosphine;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In N,N-dimethyl-formamide; at 130.0℃; for 4.0h;Inert atmosphere; Example 2 - ethyl 2-cyano-5-fluorobenzoateZinc cyanide (26.5 g; 0.225 mol) and Pd2(dba)3 (1.9 g; 3.4 mmol) were added to a solution of <strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (27.9 g; 0.112 mol) in DMF (71 ml). Triphenyl phosphine (2.9 g; 1 1 mmol) was added and then the reaction mixture was stirred at 130C under nitrogen atmosphere for 4 hours. The mixture was poured out into H2O (300 ml) and then extracted with EtOAc (200 ml). The organic layer was separated, washed with H2O (2 x 100 ml), brine (100 ml), dried (MgS04), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: hexanes/ EtOAc (5/1, v/v)). The product fractions were collected and the solvent was evaporated.Yield: 20 g (93%; orange solid).
  • 6
  • [ 139911-28-7 ]
  • [ 1384435-16-8 ]
  • 7
  • [ 139911-28-7 ]
  • [ 1384435-17-9 ]
  • 8
  • [ 139911-28-7 ]
  • [ 191171-55-8 ]
  • [ 60042-05-9 ]
YieldReaction ConditionsOperation in experiment
65% With sodium carbonate; In ethanol; at 80.0℃; for 3.0h; Example 2a. 8-fluorophenanthridin-6-ol.A mixture of m<strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (0.250 g, 1.07 mmol), 2-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)aniline (0.235 g, 1.07 mmol), palladium acetate (2.4 mg, 0.01 eq.), dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (8.81 mg, 0.021 mmol), and sodium carbonate (0.114 g, 1.073 mmol) in ethanol (5.4 mL) was heated to 80 C for 3 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was triturated with hexane, and isolated by vacuum filtration, washed with water, and dried to provide the title compound (0.15 g, 65% yield) which was used without further purification
  • 9
  • [ 139911-28-7 ]
  • [ 557-21-1 ]
  • [ 1260751-65-2 ]
YieldReaction ConditionsOperation in experiment
93% With triphenylphosphine;tris-(dibenzylideneacetone)dipalladium(0); In N,N-dimethyl-formamide; at 130.0℃; for 4.0h;Inert atmosphere; Zinc cyanide (26.5 g; 0.225 mol) and Pd2(dba)3 (1.9 g; 3.4 mmol) were added to a solution of <strong>[139911-28-7]ethyl 2-bromo-5-fluorobenzoate</strong> (27.9 g; 0.112 mol) in DMF (71 ml). Triphenyl phosphine (2.9 g; 11 mmol) was added and then the reaction mixture was stirred at 130C under nitrogen atmosphere for 4 hours. The mixture was poured out into H2O (300 ml) and then extracted with EtOAc (200 ml). The organic layer was separated, washed with H2O (2 x 100 ml), brine (100 ml), dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: hexanes/EtOAc (5/1, v/v)). The product fractions were collected and the solvent was evaporated. Yield: 20 g (93%; orange solid).
  • 10
  • [ 139911-28-7 ]
  • [ 1610927-38-2 ]
YieldReaction ConditionsOperation in experiment
47% With sodium persulfate; N-chloro-succinimide; trifluorormethanesulfonic acid; palladium diacetate; In 1,2-dichloro-ethane; at 80.0℃; for 4.0h; Compound 3 was prepared with similar procedure as compound 2. Compound 2 (1.45 g, 1.0 equiv.), NCS (0.83 g, 1.05 equiv.), Pd(OAc)2 (52.9 mg, 0.04 equiv.), Na2S2O8 (1.68 g, 1.2 equiv.), TfOH (2.6 mL, 5.0 equiv.) were used. The reaction mixture was stirred at 80 C for 4 h. Finally, compound 3 (0.78 g) was obtained in 47% yield.
  • 11
  • [ 139911-28-7 ]
  • [ 153500-76-6 ]
  • 12
  • [ 139911-28-7 ]
  • [ 1347720-31-3 ]
  • 13
  • [ 451-02-5 ]
  • [ 139911-28-7 ]
YieldReaction ConditionsOperation in experiment
70% With sodium persulfate; N-Bromosuccinimide; trifluorormethanesulfonic acid; palladium diacetate; In 1,2-dichloro-ethane; at 80.0℃; for 9.0h; Compound 1 (1.68 g, 1.0 equiv.), NBS (1.87 g, 1.05 equiv.), Pd(OAc)2 (78.5 mg, 0.035 equiv.) and Na2S2O8 (2.86 g, 1.2 equiv.) were dissolved in commercial dichloroethane (12 mL) in a 100 mL round bottom flask. Then TfOH (2.2 mL, 2.5 equiv.) was added into the reaction solution. Then the reaction mixture was stirred at 80 C for 9 h. After completion of the reaction, the mixture was cooled to room temperature and then saturated NaHCO3 was added to quench the reaction. The reaction mixture was diluted with dichloromethane and washed once with saturated aqueous NaHCO3. Then organic layer was dried over Na2SO4 and concentrated on rotavapor under reduced pressure. Finally the residue was purified by silical gel column chromatography to give compound 2 (1.71 g) in 70% yield.
  • 14
  • [ 64-17-5 ]
  • [ 394-28-5 ]
  • [ 139911-28-7 ]
  • 15
  • [ 139911-28-7 ]
  • [ 73183-34-3 ]
  • C15H19BBrFO4 [ No CAS ]
  • 16
  • [ 139911-28-7 ]
  • ethyl (5R,8R)-2-fluoro-9-oxo-5,6,7,9-tetrahydro-8H-5,8-methanobenzo[7]annulene-8-carboxylate [ No CAS ]
  • 19
  • [ 139911-28-7 ]
  • [ 141-78-6 ]
  • ethyl 3-(2-bromo-5-fluorophenyl)-3-oxopropanoate [ No CAS ]
 

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