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Structure of 835595-11-4

Chemical Structure| 835595-11-4

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Product Details of [ 835595-11-4 ]

CAS No. :835595-11-4
Formula : C6H4Cl2IN
M.W : 287.91
SMILES Code : NC1=CC=C(Cl)C(Cl)=C1I
MDL No. :MFCD28128147
InChI Key :DJDQWIYKWLGIJE-UHFFFAOYSA-N
Pubchem ID :67526267

Safety of [ 835595-11-4 ]

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

Computational Chemistry of [ 835595-11-4 ] 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 0.0
Num. H-bond donors 1.0
Molar Refractivity 53.58
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

3.15
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.

3.56
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

3.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.05

Water Solubility

Log S (ESOL):?

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

-4.05
Solubility 0.0255 mg/ml ; 0.0000884 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.

-3.37
Solubility 0.124 mg/ml ; 0.00043 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

-4.21
Solubility 0.0175 mg/ml ; 0.000061 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

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.

-5.82 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

3.0 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<0.0
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)

2.0

Application In Synthesis of [ 835595-11-4 ]

* 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 [ 835595-11-4 ]

[ 835595-11-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 95-76-1 ]
  • [ 835595-11-4 ]
  • [ 89284-72-0 ]
  • [ 220185-63-7 ]
YieldReaction ConditionsOperation in experiment
8%Chromat.; 8%Chromat.; 77%Chromat. With iodine; silver sulfate; In dichloromethane; at 20℃; for 17.0h; General procedure: The respective silver salt (0.32 g, 1 mmol) and iodine (0.25 g, 1 mmol) were typically added to a stirred solution of the benzene derivative 1a-i (1 mmol) in dichloromethane (3 mL). The reaction mixture was allowed to stir at room temperature for approximately 16 h (see refPreviewPlaceHolderTable 1, refPreviewPlaceHolderTable 2, refPreviewPlaceHolderTable 3, refPreviewPlaceHolderTable 4, refPreviewPlaceHolderTable 5 and refPreviewPlaceHolderTable 6). The reaction mixture was cooled with ice-cold water, quenched with an aqueous solution of sodium metabisulfite (0.2 mL) and, in the case of anilines, 2 M NaOH (0.2 mL). The mixture was filtered through Celite and the residue was washed with dichloromethane (3×3 mL). The combined filtrate was washed with aqueous sodium bicarbonate (3 mL), water (3 mL), and brine (3 mL). The combined organic phases were dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was redissolved in dichloromethane (10 mL) and the percent conversion of the starting material and the yields of the iodination products were determined by GC-MS using diethylene glycol di-n-butyl ether as internal standard. The relative response factor for the respective analyte (RRFA) was calculated from a calibration standard containing known amounts of the internal standard and the respective analytes using the formula RRFA=AIS·MA/(AA·MIS), where AIS is the peak area of the internal standard, AA is the area of an analyte (i.e., starting material or iodination product), MA is the mass of the analyte and MIS is the mass of the internal standard. The mass of the analyte in the reaction mixture was determined as MA=(RRFA·MIS·AA)/AIS. All samples were analyzed at least in duplicate. The iodination products of selected reactions were separated by column chromatography to obtain milligram quantities for their characterization and use as analytical standards. In the case of 3g, the isolated quantities were not sufficient for 13C NMR analysis.
  • 2
  • [ 835595-11-4 ]
  • 5-[6-[(4-tert-butyl-3-fluorophenyl)sulfonylamino]-2,3-dichlorophenyl]quinoline-8-carboxylic acid [ No CAS ]
  • 3
  • [ 835595-11-4 ]
  • [ 1452184-05-2 ]
  • 4-tert-butyl-N-(3,4-dichloro-2-iodophenyl)-3-fluorobenzsulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% [0106] (a) To a solution of <strong>[835595-11-4]3,4-dichloro-2-iodoaniline</strong> (example 2, 2.2 g, 7.67 mmol) in dry pyridine (8 mL) was added 4-tert-butyl-3-fluorophenylsulfonyl chloride (2.11 g, 8.43 mmol) and the reaction mixture was heated at 80 0 C for overnight. LCMS indicated presence of mono and bis-sulfonamides. 10 N aq. NaOH (3 mL) and ethanol (2 mL) were added to hydrolyze the bis-sulfonamide. The reaction mixture was then heated at 80 C for 2 h. It was cooled to r.t, excess solvent was removed in vacuo to afford a dark brown solid, diluted with DCM, washed with IN aq.HCl, and purified by flash column using hexanes: ethyl acetate mixture as an eluent on silica column to get the pure 4-tert-butyl-N-(3,4-dichloro-2- iodophenyl)-3-fluorobenzsulfonamide as an off white solid (3.5 g, 91%)
  • 4
  • [ 95-76-1 ]
  • [ 835595-11-4 ]
YieldReaction ConditionsOperation in experiment
15% With hydrogen iodide; dihydrogen peroxide; In water; at 20℃;Darkness; [0092] To a stirred suspension of 3,4-dichloroaniline (20 g, 123 mmol), HI (48%>, 15.7 g, 123 mmol), H202 (30%, 8.3 g, 246 mmol) in H20 (62 mL) at r.t. The reaction mixture was stirred in dark at r.t for overnight. The supernatant was discarded, diluted with ethyl acetate: hexanes (1 : 10), quenched with saturates NaHS03, stirred for 1 h at ambient temperature, filtered the solids. The filtrate was washed with water, saturated aqueous NaHC03, dried (Na2S04), filtered and concentrated to get 1 :4 regioisomeric mixture of iodo derivative (minor isomer is required). It was recrystallized from cyclohexane to afford 1 : 1 mixture of regioisomers enriched in the filtrate. This mixture was further purified by flash column chromatography on silica gel, eluting with ethyl acetate :hexanes (0-2%) to get the required compound as a cream color solid (5.2 g, -15% yield). 1H NMR (400 MHz, CDC13) delta 7.22 (d, J= 8.6 Hz, 1 H), 6.60 (d, J= 8.6 Hz, 1 H), 4.32 (br, 2 H).
 

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