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Chemical Structure| 1007-15-4 Chemical Structure| 1007-15-4
Chemical Structure| 1007-15-4

3'-Bromo-4'-fluoroacetophenone

CAS No.: 1007-15-4

4.5 *For Research Use Only !

Cat. No.: A147307 Purity: 98%

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Product Details of [ 1007-15-4 ]

CAS No. :1007-15-4
Formula : C8H6BrFO
M.W : 217.04
SMILES Code : C1=C(C(=CC=C1C(C)=O)F)Br
MDL No. :MFCD00042466
InChI Key :SZDWTGAORQQQGY-UHFFFAOYSA-N
Pubchem ID :70508

Safety of [ 1007-15-4 ]

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

Calculated chemistry of [ 1007-15-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 44.29
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.03
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

2.4
Log Po/w (WLOGP)?

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

3.21
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.

2.94
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

3.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.76

Water Solubility

Log S (ESOL):?

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

-3.04
Solubility 0.2 mg/ml ; 0.000922 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.

-2.4
Solubility 0.864 mg/ml ; 0.00398 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

-3.87
Solubility 0.0291 mg/ml ; 0.000134 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.

-5.92 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

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<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)

1.52

Application In Synthesis of [ 1007-15-4 ]

* 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 [ 1007-15-4 ]

[ 1007-15-4 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1007-15-4 ]
  • [ 73183-34-3 ]
  • [ 765916-70-9 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate; In 1,4-dioxane; dimethyl sulfoxide; 1-[4-Fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]ethanone To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46.07 mmol) and bis(pinacolato)diboron (12.87 g, 50.68 mmol) in 1,4-dioxane (90 ml) and DMSO (10 ml) was added potassium acetate (9.04 g, 92.14 mmol) and the mixture degassed for 1 h. Dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane (DCM) adduct (1.13 g, 1.38 mmol) was added and the mixture degassed for a further 15 min and then heated at 90 C. for 18 h. After cooling to ambient temperature the mixture was filtered and the filter cake washed with ethyl acetate (2*50 ml). The filtrate was then washed with water (100 ml), brine (100 ml), dried (MgSO4), filtered and evaporated to give the title product as a brown oil which was used without further purification (12.0 g): δH (400 MHz, CDCl3) 1.38 (12H, s), 2.61 (2H, s), 2.61 (3H, s), 7.10 (1H, t, J 8.6 Hz), 8.05-8.09 (1H, m), 8.35 (1H, dd, J 2.3, 5.5 Hz).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110.0℃; for 0.166667h;Microwave irradiation; General procedure: To 2 mL of 1,4-dioxane in microwave reaction vessel were added bromobenzene (0.20 g, 1.27 mmol), bis(pinacolato)diboron (0.36 g, 1.40 mmol), potassium acetate (0.38 g, 3.8 mmol), and PdCl2(dppf) (0.028 g, 0.038 mmol). The reaction mixture was heated to 110 C by microwave irradiation at power 100 W for 10 min. After solvent was removed under reduced pressure, the residue was purified by dry column vacuum chromatography (DCVC) using dichloromethane (DCM) as eluent provided the 0.16 g in 62 % yield;
  • 2
  • [ 50638-47-6 ]
  • [ 1007-15-4 ]
  • C15H13BrClFO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1-Bromo-3-[1-(4-methoxy-3-chlorophenyl)-vinyl]-6-fluorobenzene A solution of n-butyllithium (1.6 M solution in hexane, 20 mL, 1.1 eq) was added dropwise to a solution of <strong>[50638-47-6]4-bromo-2-chloro-1-methoxy-benzene</strong> (6 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) at -78 C. After stirring 30 min 3-bromo-4-fluoroacetophenone (5.8 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) was added dropwise. The mixture was allowed to warm up to room temperature and stirred for 2 h, then treated with water (10 mL), extracted with ethyl acetate, dried (sodium sulfate) and concentrated in vacuo. The crude was dissolved in acetic acid (80 mL) and concentrated sulfuric acid (17 mL) was added. The mixture was warmed to 75 C. for 30 min, cooled at room temperature and neutralized with 1 N NaOH. The aqueous phase was extracted with dichloromethane (3*100 mL), dried (sodium sulfate) the solvent was removed under reduced pressure. The residue was purified by column chromatography (cyclohexane) to afford the title compound as a colourless oil (3.2 g, 36%); Mass (calculated) C15H11BrClFO [341]; (found) [M+H+]=342 LC Rt=3.05 min (5 min method) 1H-NMR (CDCl3): 3.90 (s, 3H), 5.35 (d, 2H), 6.88 (m, 1H), 7.06-7.26 (m, 4H), 7.50 (m, 1H)
 

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