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Chemical Structure| 57381-39-2 Chemical Structure| 57381-39-2

Structure of 57381-39-2

Chemical Structure| 57381-39-2

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Product Details of [ 57381-39-2 ]

CAS No. :57381-39-2
Formula : C7H3BrFN
M.W : 200.01
SMILES Code : C1=C(C(=CC=C1F)Br)C#N
MDL No. :MFCD00142875
InChI Key :MDHNVHCZDCSTMS-UHFFFAOYSA-N
Pubchem ID :93654

Safety of [ 57381-39-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Computational Chemistry of [ 57381-39-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.81
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.89
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

2.43
Log Po/w (WLOGP)?

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

2.88
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.

2.63
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

2.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.55

Water Solubility

Log S (ESOL):?

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

-3.05
Solubility 0.176 mg/ml ; 0.000881 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.

-2.57
Solubility 0.535 mg/ml ; 0.00268 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

-3.62
Solubility 0.0481 mg/ml ; 0.00024 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.

-5.79 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)

1.67

Application In Synthesis of [ 57381-39-2 ]

* 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 [ 57381-39-2 ]

[ 57381-39-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 765916-70-9 ]
  • [ 13716-12-6 ]
  • [ 57381-39-2 ]
  • [ 765916-69-6 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride;tris(dibenzylideneacetone)dipalladium (0); In tetrahydrofuran; 2-Methylpentane; water; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; ethyl acetate; 5'-Acetyl-4,2'-difluorobiphenyl-2-carbonitrile To a degassed solution of 1-[4-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]ethanone (12 g, 45.43 mmol), 2-bromo-5-fluorobenzonitrile (9.09 g, 5.28 ml, 45.44 mmol), potassium fluoride (7.92 g, 136.31 mmol) and tris(dibenzylideneacetone)palladium(0) (0.834 g, 0.908 mmol) in THF (200 ml) and water (10 ml) was added tri-tert butylphosphine (10% weight solution) (0.368 g, 3.63 ml, 1.817 mmol). The reaction was heated at 70 C. for 14 h then allowed to cool to ambient temperature. The reaction was partitioned between water (200 ml) and ether (300 ml). The aqueous phase was extracted with ether (150 ml) and the combined organics washed with brine (200 ml), dried (MgSO4), filtered and evaporated to give a brown solid. The solid was dissolved in DCM and adsorbed onto silica. The crude product was chromatographed on silica (5-20% EtOAc in isohexane) to give the title product as a white solid (6.8 g): δH (400 MHz, CDCl3) 2.63 (3H, s), 7.31 (1H, t, J 9.0 Hz), 7.40-7.44 (1H, m), 7.50-7.53 (2H, m), 8.02-8.10 (2H, m).
  • 2
  • [ 75-16-1 ]
  • [ 57381-39-2 ]
  • [ 1006-33-3 ]
YieldReaction ConditionsOperation in experiment
45% 33a 33bTo a solution of 2-bromo-5-fluoro-benzonitrile 33a (10 g, 50 mmol) in dry tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2 M in ether, 19 mL, 60.0 mmol), and the resulting mixture was heated to reflux for 4 hours. The RM was then cooled down to RT, poured into a 2 N HCl solution (100 mL) and then diluted with methanol (100 mL). The resulting green solution was concentrated on a steam bath for 1 h at which point the organic solvents had been removed and the crude product had precipitated. The reaction mixture was then extracted with ethyl acetate, dried over MgSO4 and concentrated. The residue was purified by column chromatography using heptane and dichloromethane to give 4.88 g (45% yield) of the desired product l-(2-bromo-5-fluorophenyl)ethanone 33b as a pink oil; m/z 218 [M+H]+.
45% In tetrahydrofuran; diethyl ether; for 4h;Inert atmosphere; Reflux; To a solution of 2-bromo-5-fluorobenzonitrile (10.0 g, 48.5 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2M in ether, 19 mL, 60.0 mmol). The resulting mixture was heated to reflux for 4 h. The reaction mixture was then cooled, poured into 2N hydrochloric acid (100 mL), and diluted with methanol (100 mL). The organic solvents were removed and the crude product precipitated out. The reaction mixture was extracted with ethyl acetate, dried over MgS04, and concentrated. The residue was purified by column chromatography (heptane/dichloromethane) to give 4.88 g (21.9 mmol, 45percent) of compound 86 as a pink oil.
45% In tetrahydrofuran; diethyl ether; for 4h;Reflux; To a solution of 2-bromo-5-fluorobenzonitrile (10.0 g, 48.5 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2M in ether,19 mL, 60.0 mmol). The resulting mixture was heated to reflux for 4 h. The reaction mixture was then cooled, poured into 2N hydrochloric acid (100 mL), and diluted with methanol (100 mL). The organic solvents were removed and the crude product precipitated out. The reaction mixture was extracted with ethyl acetate, dried over MgSO4, and concentrated. The residue was purified by column chromatography (heptane/dichioromethane) to give 4.88 g (21.9 mmol, 45percent)of compound 86 as a pink oil.
  • 3
  • [ 57381-39-2 ]
  • [ 747392-34-3 ]
YieldReaction ConditionsOperation in experiment
55.5% With sodium tetrahydroborate; trifluoroacetic acid; In tetrahydrofuran; at 20℃; for 16h; To a solution of 2-bromo-5-fluorobenzonitrile (3.0g, 15.00mmol) and NaBH4 (1.419 g, 37.5 mmol) in THF (30mL) was slowly added TFA (3.47 ml., 45.0 mmol) over a period of20 min. The resulting mixture was stirred at rt for 16 hours, then MeOH (10 mL) was added and the mixture wasstirred for another 30 min. It was then diluted with EtOAc(200 ml.), washed with water, dried over Na2S04 and evaporated.The residue was purified on an 80 g Thompson silicacartridge (3% to 100% B in Hexanes, 1200 ml., B: 10%MeOH in EtOAc). The desired product was obtained as acolorless oil (1.70 g, 8.33 mmol, 55.5% yield).
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Blaise Reaction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • 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 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 • Ritter 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 • Thorpe-Ziegler Reaction • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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