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Chemical Structure| 105946-82-5 Chemical Structure| 105946-82-5

Structure of 105946-82-5

Chemical Structure| 105946-82-5

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Product Details of [ 105946-82-5 ]

CAS No. :105946-82-5
Formula : C12H8BrI
M.W : 359.00
SMILES Code : IC1=CC=C(C2=CC=C(Br)C=C2)C=C1
MDL No. :MFCD17676204
InChI Key :GWOAJJWBCSUGHH-UHFFFAOYSA-N
Pubchem ID :10904452

Safety of [ 105946-82-5 ]

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

Computational Chemistry of [ 105946-82-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 72.3
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.

3.0
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

5.61
Log Po/w (WLOGP)?

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

4.72
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.

5.33
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

5.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.77

Water Solubility

Log S (ESOL):?

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

-6.17
Solubility 0.000244 mg/ml ; 0.000000679 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.37
Solubility 0.00152 mg/ml ; 0.00000424 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-6.67
Solubility 0.0000768 mg/ml ; 0.000000214 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly 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

Yes
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

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.

-4.51 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

2.0
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)

2.15

Application In Synthesis of [ 105946-82-5 ]

* 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 [ 105946-82-5 ]

[ 105946-82-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 135-88-6 ]
  • [ 105946-82-5 ]
  • [ 352359-42-3 ]
YieldReaction ConditionsOperation in experiment
62% With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; at 90℃; for 3h; Synthesis Example 6: Synthesis of Intermediate 6 16.2 g (45 mmol) of 4-bromo-4'-iodo-biphenyl, 6.58 g (30 mmol) of N-phenyl-2-naphthylamine, 4.3 g (45 mmol) of t-BuONa, 0.55 g (0.6 mmol) of Pd2(dba)3, and 0.12 g (0.6 mmol) of P(t-Bu)3 were dissolved in 100 mL of toluene and stirred at 90C for 3 hours. After the reaction was completed, the reaction product was cooled to room temperature and extracted three times with distilled water and 100 ml of diethylether. An organic layer was collected and dried using magnesium sulfate to evaporate the solvent. The residue was separated and purified using silica gel column chromatography to obtain 8.38 g (yield: 62%) of Intermediate 6. This compound was identified using HR-MS. C28H20BrN calc.: 449.0779; and found: 449.0775.
  • 2
  • [ 105946-82-5 ]
  • potassium ferrocyanide [ No CAS ]
  • [ 57774-35-3 ]
  • 3
  • [ 90-30-2 ]
  • [ 105946-82-5 ]
  • [ 352359-42-3 ]
YieldReaction ConditionsOperation in experiment
66% With copper; potassium carbonate; sodium sulfate; In nitrobenzene; The starting material, N-phenylnaphthalen-1-amine (65.8g, 300mmol) in 4-bromo-4'-iodo-1,1'-biphenyl (129.2g, 360mmol), Na2SO4 (42.6g, 300mmol), K2CO3 (41.4 g, 300mmol), Cu (5.72g, 90mmol), to the use of the nitrobenzene product synthesis example 89.2g (yield 66% was obtained).
66% With copper; potassium carbonate; sodium sulfate; In nitrobenzene; at 200℃; Starting material, N-phenylnaphthalen-1-amine (65.8 g, 300 mmol), 4-bromo-4'-iodo-1,1'-biphenyl (129.2 g, 360mmol), Na2SO4 (42.6 g, 300 mmol), K2CO3 (41.4 g, 300 mmol), Cu (5.72 g, 90 mmol), nitrobenzene was obtained using the synthesis method of Sub 1-1 of Example 2 above to obtain 89.2 g of product (yield: 66%).
  • 4
  • [ 870119-58-7 ]
  • [ 105946-82-5 ]
  • C30H20BrN [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 4h; P2 (60 g, 1 eq), 4-bromo-4'-iodo-1,1'-biphenyl (4-bromo-4'-iodo-1,1'-biphenyl) (63 g, 1.3 eq) Pd (PPh3) 4 (7.8 g, 0.05 eq), K2CO3 (28 g, 1.5 eq), toluene (toluene) 600 ml, ethanol (Ethanol) 100 ml, H2O 100ml Is placed in a round bottom flask (1-neck-R.B.F.) and stirred. (4h) MC hot filter was performed twice to obtain intermediate (1). (33 g, Step yield = 54%)
  • 5
  • [ 105946-82-5 ]
  • 2,2‐difluoro‐2‐(triphenylphosphonio)acetate [ No CAS ]
  • [ 57774-35-3 ]
  • [ 57774-34-2 ]
YieldReaction ConditionsOperation in experiment
With copper nitrate hemi(pentahydrate); 4,4'-bis(carbomethoxy)-2,2'-bipyridine; sodium amide; In N,N-dimethyl-formamide; at 130℃; for 15h; General procedure: Under air atmosphere, a reaction tube was charged with aryl iodides (0.5 mmol), Ph3P+CF2CO2- (268 mg, 0.75 mmol, 1.5equiv), L4 (6.3 mg, 5 mol %), Cu (NO3)2·2.5H2O (143 mg, 0.65 mmol, 1.3 equiv), NaNH2 (39 mg, 1.0 mmol, 2.0 equiv) and dry DMF (4 mL). The resulting mixture was stirred at 130C for 15 h. After being cooled to room temperature, the mixture was filtered through a pad of Celite. The solid was washed with DCM, and the combined organic phase was washed with water (15 mL × 3). The organic layer was further washed with saturated sodium sulfite and saturated brine, and then dried with sodium sulfate. After the solvent was removed by concentration under vacuum, the residue was subjected to flash column chromatography to afford the final product.
 

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