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Structure of 1256945-00-2

Chemical Structure| 1256945-00-2

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Product Details of [ 1256945-00-2 ]

CAS No. :1256945-00-2
Formula : C7H3BrF3I
M.W : 350.90
SMILES Code : FC(C1=CC=C(Br)C=C1I)(F)F
MDL No. :MFCD21603817
Boiling Point : No data available
InChI Key :PGFPLTAEOHMUKY-UHFFFAOYSA-N
Pubchem ID :49834559

Safety of [ 1256945-00-2 ]

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

Computational Chemistry of [ 1256945-00-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 51.86
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.

2.5
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

4.15
Log Po/w (WLOGP)?

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

5.22
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.

4.94
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

4.49
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.26

Water Solubility

Log S (ESOL):?

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

-4.93
Solubility 0.00408 mg/ml ; 0.0000116 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.

-3.86
Solubility 0.0487 mg/ml ; 0.000139 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

-5.04
Solubility 0.00316 mg/ml ; 0.00000902 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

No
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.

-5.49 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

1.0 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)

1.89

Application In Synthesis of [ 1256945-00-2 ]

* 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 [ 1256945-00-2 ]

[ 1256945-00-2 ] Synthesis Path-Downstream   1~9

  • 2
  • [ 703-91-3 ]
  • [ 1256945-00-2 ]
YieldReaction ConditionsOperation in experiment
68% Preparation 12 4-Bromo-2-iodo-1-trifluoromethyl-benzene To a stirred solution of 5-bromo-2-(trifluoromethyl) aniline (300 mg, 1.255 mM) in dry THF (10 mL) was added BF3-etherate (707 mg, 5.02 mM) and tert-butyl nitrite (452 mg, 4.39 mM) at -78 C. Reaction mixture was stirred for 10 min, warmed to room temperature and maintained for 30 min. The reaction mixture was diluted with diethyl ether (30 mL). The solid was filtered off and dried under vacuum. This diazonium salt was added to a mixture of KI (289 mg, 1.746 mM) and iodine (203 mg, 0.876 mM) in acetone taken in an another flask at 0 C. and stirred at room temperature for 1 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The obtained residue was diluted with water (20 mL) and the product was extracted with diethyl ether (2*20 mL). The combined organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the title compound as a liquid (230 mg, 68%). 1H NMR (400 MHz, CDCl3) delta 8.19 (s, 1H), 7.59 (d, 1H), 7.50 (d, 1H).
  • 3
  • [ 1256945-00-2 ]
  • [ 292638-85-8 ]
  • 3-(5-bromo-2-(trifluoromethyl)phenyl)acrylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With potassium carbonate; triethylamine;palladium diacetate; triphenylphosphine; In tetrahydrofuran; at 80℃; for 16h;Sealed tube; Preparation 13 3-(5-Bromo-2-trifluoromethyl-phenyl)-acrylic acid methyl ester To a stirred solution of triphenylphosphine (486 mg, 1.857 mM) and Palladium acetate (159.9 mg, 0.714 mM) in dry THF taken in a sealed tube was added triethylamine (0.4 mL, 2.857 mM) at room temperature. Reaction mixture was degassed for 10 min, and then stirred for 15 min. To this 4-Bromo-2-iodo-1-(trifluoromethyl)benzene, methylacrylate (157 mg, 1.57 mM) were added followed by the addition of potassium carbonate (394 mg, 2.887 mM) at RT. Reaction mixture was heated to 80 C. for 16 h. After completion of reaction, reaction mixture was cooled to room temperature and passed through celite bed, washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0-5% ethyl acetate in pet ether) to afford the title compound as a solid (200 mg, 76%). 1H NMR (400 MHz, CDCl3) delta 7.96 (d, 1H), 7.82 (s, 1H), 7.62 (d, 1H), 7.56 (d, 1H), 6.40 (d, 1H), 3.80 (s, 3H).
  • 4
  • [ 1256945-00-2 ]
  • C15H11F3OS [ No CAS ]
  • 5
  • [ 1256945-00-2 ]
  • C15H15F3OS [ No CAS ]
  • 6
  • [ 1256945-00-2 ]
  • C18H21F3OS [ No CAS ]
  • 7
  • [ 1256945-00-2 ]
  • C30H47F3OSSn [ No CAS ]
  • 8
  • [ 1256945-00-2 ]
  • C42H40F6N4O2S4 [ No CAS ]
  • 9
  • [ 1256945-00-2 ]
  • [ 927-74-2 ]
  • C11H8BrF3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.5 g With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine; In tetrahydrofuran; at -30 - 20℃; for 19h; Into a glass reaction vessel equipped with a stirrer and a capacity of 200 mL,3.51 g of 4-bromo-2-iodo-1- (trifluoromethyl) benzene(10.0 mmol), 67 mL of dehydrated tetrahydrofuran,8.4 mL (60.0 mmol) of diisopropylamine,701.9 mg (1.0 mmol) of dichlorobis (triphenylphosphine) palladium (II), 190.5 mg (1.0 mmol) of copper (I) iodide) Was added, and while keeping the internal temperature at -30 C., 832 muL of 3-butyn-1-ol(11.0 mmol) were added, followed by reaction at room temperature for 19 hours.The solvent was distilled off under reduced pressure, and a saturated aqueous solution of ammonium chloride was added to the resulting reaction crude productThe mixture was extracted with diethyl ether, dried over magnesium sulfate and the solvent was distilled off under reduced pressure,Silica gel column chromatography (hexane: ethyl acetate = 8: 2)To obtain 2.5 g of compound (C14-e) as a pale yellow solid.
 

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