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Chemical Structure| 123158-75-8 Chemical Structure| 123158-75-8

Structure of 123158-75-8

Chemical Structure| 123158-75-8

4-Chloro-2-iodo-6-nitroaniline

CAS No.: 123158-75-8

4.5 *For Research Use Only !

Cat. No.: A110708 Purity: 95%

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Product Details of [ 123158-75-8 ]

CAS No. :123158-75-8
Formula : C6H4ClIN2O2
M.W : 298.47
SMILES Code : NC1=C([N+]([O-])=O)C=C(Cl)C=C1I
MDL No. :MFCD23115369
InChI Key :WDQPNLNIJFQQRL-UHFFFAOYSA-N
Pubchem ID :12143564

Safety of [ 123158-75-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 123158-75-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 57.4
TPSA ?

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

71.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.62
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

2.9
Log Po/w (WLOGP)?

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

2.44
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.

1.8
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

0.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.88

Water Solubility

Log S (ESOL):?

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

-3.82
Solubility 0.045 mg/ml ; 0.000151 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.

-4.07
Solubility 0.0255 mg/ml ; 0.0000853 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

-2.98
Solubility 0.316 mg/ml ; 0.00106 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

No
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.

-6.06 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

0.0
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

4.0 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)

2.56

Application In Synthesis of [ 123158-75-8 ]

* 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 [ 123158-75-8 ]

[ 123158-75-8 ] Synthesis Path-Downstream   1~31

  • 2
  • [ 123158-75-8 ]
  • [ 108-24-7 ]
  • [ 64-19-7 ]
  • acetic acid-(4-chloro-2-iodo-6-nitro-anilide) [ No CAS ]
  • 3
  • [ 89-63-4 ]
  • [ 123158-75-8 ]
YieldReaction ConditionsOperation in experiment
69% With iodine; silver nitrate; In ethanol; at 20℃; for 8h; (Step 1)Commercially available 4-chloro-2-nitro-phenylamine (17.4 g, 131.5 mmol) was dissolved in ethanol (300 mL), and thereto silver nitrate (27 g, 157.7 mmol) and iodine (40 g, 157.7 mmol) were added. The mixture was stirred for 8 hours at room temperature. At the end of reaction, the mixture was filtered using celite and washed with 100 ml of ethylacetate and concentrated. To the concentrate, added water and extracted with ethylacetate. The organic layer was washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate to give 2-amino-5-chloro-3-nitro-phenyliodide (27.4 g, Yield 69%).1H-NMR (500 MHz, CDCl3); delta 7.94 (s, 1H), 7.75 (s, 1H), 6.48 (br s, 2H), 2.23 (s, 3H)
28% With Iodine monochloride; In glacial AcOH; A. Synthesis of 4-chloro-2-iodo-6-nitroaniline: The procedure of Leeson, P. D. et al. (J. Med. Chem. 34:1243-1252 (1991)) was adapted. To a solution of 4-chloro-2-nitroaniline (2.15 g, 12.45 mMol, Aldrich, used as received) in glacial AcOH (16 mL) was added iodine monochloride (2.114 g, 12.90 mMol, Aldrich). The mixture was heated at 120 C. for 5 h, then cooled and poured into ice water (30 g). The precipitate was collected and washed with 10% sodium sulfite solution (20 mL), then it was crystallized from MeOH to give 4-chloro-2-iodo-6-nitroaniline (1.05 g, 28%), as long brown needles, m.p. 134-5 C. NMR (1 H, CDCl3): delta6.660 (s, 2H); 7.906 (d, 1H, J=2.1 Hz); 8.188 (d, 1H, J=1.8 Hz).
With Iodine monochloride; In acetic acid; a) A solution of 4-chloro-2-nitroaniline (34.5 g) in acetic acid (500 ml) was refluxed with iodine monochloride (65.0 g) for 7 h with stirring, then was cooled and added to excess water. The precipitate was filtered off, washed with aqueous sodium sulphite and after column chromatography yielded 4-chloro-2-iodo-6-nitroaniline (8.5 g). delta (360 MHz, DMSO-d6) 7.13 (2H, bs, NH2), 8.08 (1H, d, 3-H) and 8.13 (1H, d, 5-H).
  • 4
  • [ 64-17-5 ]
  • [ 123158-75-8 ]
  • [ 110-46-3 ]
  • [ 123158-76-9 ]
  • 5
  • [ 64-19-7 ]
  • [ 89-63-4 ]
  • p-toluenesulfonylacid dichloroamide [ No CAS ]
  • sodium iodide [ No CAS ]
  • [ 123158-75-8 ]
  • 6
  • [ 123158-75-8 ]
  • [ 4637-24-5 ]
  • N'-(4-chloro-2-iodo-6-nitrophenyl)-N,N-dimethylimidoformamide [ No CAS ]
  • 7
  • [ 123158-75-8 ]
  • N-(6-chloro-4-iodo-1H-benzimidazol-2-yl)-N,N-dimethylamine [ No CAS ]
  • 8
  • [ 123158-75-8 ]
  • [ 83171-49-7 ]
  • 9
  • [ 123158-75-8 ]
  • [ 123157-61-9 ]
  • 10
  • [ 123158-75-8 ]
  • [ 123157-60-8 ]
  • 11
  • [ 123158-75-8 ]
  • [ 123158-45-2 ]
  • 12
  • [ 123158-75-8 ]
  • [ 123158-44-1 ]
  • 13
  • [ 88-74-4 ]
  • [ 123158-75-8 ]
  • 14
  • [ 71-23-8 ]
  • [ 123158-75-8 ]
  • [ 153505-43-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;Pb-CaCO3; In tetrahydrofuran; Example B4 Preparation of 4-chloro-6-iodo-1.2-phenylenediamine 1.5 g of <strong>[123158-75-8]4-chloro-2-iodo-6-nitroaniline</strong> together with 50 ml of tetrahydrofuran and 10 ml of 1-propanol are initially introduced into a stirred autoclave. 5 mg of FeCl2.4H2 O and 0.3 g Pt/Pb-CaCO3 catalyst are added to the solution, and hydrogenation is carried out at 130 C. and 20 bar of hydrogen. After the hydrogenation has come to a standstill, the reaction mixture is cooled to room temperature, the reactor is rendered inert with nitrogen and the catalyst is filtered off. After filtration, the solvent is removed by distillation to give 1.3 g of 4-chloro-6-iodo-1,2-phenylenediamine as a crude product. 1 H-NMR (CDCI3, 300MHz) 3.56 ppm (s, 2H, broad); 3.77 ppm (s, 2H, broad); 6.68 ppm (s, 1H); 7.18 ppm (s, 1H).
YieldReaction ConditionsOperation in experiment
With iodine; silver nitrate; In ethanol; at 20℃; for 8h; General procedure: Commercially available 4-methyl-2-nitro-phenylamine (20 g, 131.5 mmol) was dissolved in ethanol (300 mL), silver nitrate (27 g, 157.7 mmol) and iodine (40 g, 157.7 mmol) were added thereto, and the mixture was stirred for 8 h at room temperature. After completion of the reaction, the reaction mixture was filtered through a cellite, washed with 100 mL of ethyl acetate, and concentrated. Water was added to the residue, which was then extracted with ethyl acetate, washed with saturated sodium chloride solution, and dried over anhydrous magnesium sulfate to give the title compound (29 g, Yield 69%).
With iodine; silver nitrate; In ethanol; at 20℃; for 8h; General procedure: Commercially available 4-methyl-2-nitro - phenylamine (20g, 131.5mmol) was dissolved in ethanol (300mL), was added silver nitrate (27g, 157.7mmol) and iodine (40g, 157.7mmol), in It was stirred at room temperature for 8 hours. After completion of the reaction, the Cellite filtration, washing with ethyl acetate 100mL was concentrated. After addition of water and extracted with ethyl acetate. After washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and the harvest of the title compound (29g, yield 69%).
With iodine; silver nitrate; In ethanol; at 20℃; for 8h; General procedure: Commercially available 4-methyl-2-nitro-phenylamine (20 g, 131.5 mmol) was dissolved in ethanol (300 ml), to which were added silver nitrate (27 g, 157.7 mmol) and iodine (40 g, 157.7 mmol), and the mixture was stirred at room temperature for 8 hours. After completion of the reaction, the mixture was filtered through Cellite, washed with ethyl acetate (100 ml), and concentrated. The reactant was added with water, extracted with ethyl acetate, washed with saturated sodium chloride solution, and dried with anhydrous magnesium sulfate to give the title compound (29 g, Yield 69%).
  • 16
  • [ 123158-75-8 ]
  • [ 2170-06-1 ]
  • [ 1120334-15-7 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 3h; <strong>[123158-75-8]2-Amino-5-chloro-3-nitro-phenyliodide</strong> (1.5 g, 4.90 mmol) prepared in <n="51"/>Preparation 19 and l-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 rnL). Palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added thereto, and the mixture was stirred under heating for 3 h to 100C . After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (1.05 g, Yield 87%). 1H-NMR (400HMz, CDCl3); delta 9.78(br s, IH), 8.15(s, IH), 7.78(s, IH),7.38~7.48(m, 5H), 0.26(s, 9H)
87% With triethylamine; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 3h; Preparation 41: 5-Chloro-3-phenyl-7-nitro-1H-indoleStep A: 5-Chloro-7-nitro-3-phenyl-2-trimethylsilyl-1H-indole; <strong>[123158-75-8]2-Amino-5-chloro-3-nitro-phenyliodide</strong> (1.5 g, 4.90 mmol) prepared in Preparation 19 and 1-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 mL). Palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added thereto, and the mixture was stirred under heating for 3 h to 100 C. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (1.05 g, Yield 87%).1H-NMR (400 MHz, CDCl3); delta 9.78(br s, 1H), 8.15(s, 1H), 7.78(s, 1H), 7.387.48(m, 5H), 0.26(s, 9H)
87% With triethylamine; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 3h; (Step 2)<strong>[123158-75-8]2-Amino-5-chloro-3-nitro-phenyliodide</strong> (1.5 g, 4.90 mmol) obtained in Step 1 and 1-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 mL), and thereto palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added. The mixture was heated under stirring for 3 hours at 100 C. At the end of reaction, added water and extracted with ethylacetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure and the residue was separated by column chromatography to give 5-chloro-7-nitro-3-phenyl-2-trimethylsilyl-1H-indole (1.05 g, Yield 87%).1H-NMR (400 MHz, CDCl3); delta 9.78 (br s, 1H), 8.15 (s, 1H), 7.78 (s, 1H), 7.387.48 (m, 5H), 0.26 (s, 9H)
87% With palladium diacetate; triethylamine; lithium chloride; In N,N-dimethyl-formamide; at 100℃; for 3h; <strong>[123158-75-8]2-Amino-5-chloro-3-nitro-phenyliodide</strong> (1.5 g, 4.90 mmol) prepared in Preparation 19 and 1-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 mL). Palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added thereto, and the mixture was stirred under heating for 3 h to 100 C. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (1.05 g, Yield 87%).

  • 17
  • [ 931-49-7 ]
  • [ 123158-75-8 ]
  • [ 1180556-79-9 ]
  • 18
  • [ 628-71-7 ]
  • [ 123158-75-8 ]
  • [ 1180556-81-3 ]
  • 19
  • [ 766-83-6 ]
  • [ 123158-75-8 ]
  • [ 1180556-78-8 ]
  • 20
  • [ 123158-75-8 ]
  • [ 693-02-7 ]
  • [ 1180556-77-7 ]
  • 21
  • [ 123158-75-8 ]
  • [ 693-02-7 ]
  • [ 1180556-80-2 ]
  • 22
  • [ 123158-75-8 ]
  • [ 407-25-0 ]
  • [ 1174672-63-9 ]
YieldReaction ConditionsOperation in experiment
95% With pyridine; In tetrahydrofuran; at 0 - 20℃; for 9h; (Step 1)2-Iodo-4-chloro-6-nitro-phenylamine (10.0 g, 33.50 mmol) of was dissolved in 200 ml of tetrahydrofuran, and 3.97 g (50.25 mmol) of pyridine and 7.74 g (36.85 mmol) of trifluoroacetic anhydride were added. The mixture was stirred for 9 hours at 0 C.room temperature. At the end of reaction, the reaction mixture was diluted with water and extracted with ethylacetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and separated by column chromatography to obtain trifluoroacetamide 12.3 g (Yield 85%).
  • 23
  • [ 696-59-3 ]
  • [ 123158-75-8 ]
  • C10H6ClIN2O2 [ No CAS ]
  • 24
  • [ 123158-75-8 ]
  • (7-chloro-4-methyl-9-nitropyrrolo[1,2-a]quinolin-5-yl)diphenylphosphine oxide [ No CAS ]
  • 25
  • [ 123158-75-8 ]
  • diethyl (7-chloro-4-methyl-9-nitropyrrolo[1,2-a]quinolin-5-yl)phosphonate [ No CAS ]
  • 26
  • [ 123158-75-8 ]
  • 3-(5-chloro-3-nitro-2-(1H-pyrrol-1-yl)phenyl)prop-2-yn-1-ol [ No CAS ]
  • 27
  • [ 123158-75-8 ]
  • [ 2170-06-1 ]
  • [ 1120334-14-6 ]
  • 28
  • [ 123158-75-8 ]
  • SnCl2 ·2H2 O [ No CAS ]
  • [ 153505-43-2 ]
YieldReaction ConditionsOperation in experiment
336 mg (96%) In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; B. Synthesis of 4-chloro-6-iodo-1,2-phenylenediamine: To a stirred mixture of <strong>[123158-75-8]4-chloro-2-iodo-6-nitroaniline</strong> (389 mg, 1.305 mMol) in ethanol (10 mL) was added SnCl2 ·2H2 O (1.468 g, 6.526 mMol) in one portion. The mixture was refluxed at 80 C. (oil bath 90 C.) with stirring for 0.5 h to form a clear solution and then refluxing was continued for another 0.5 h. The solution was cooled to room temperature and ice water (20 g) was added. The pH was adjusted to pH~7 and the mixture was extracted with ethyl acetate. The extract was dried over MgSO4, and evaporated to dryness to give 336 mg (96%) of 4-chloro-6-iodo-1,2-phenylenediamine, as a brown solid. NMR (1 H, CDCl3): delta3.536 (s, 2H); 3.763 (s, 2H); 7.165 (d, 1H, J=1.8 Hz); 6.671 (d, 1H, J=1.8 Hz).
  • 29
  • [ 123158-75-8 ]
  • [ 153505-24-9 ]
  • 30
  • [ 123158-75-8 ]
  • 5-Iodo-6-nitro-7-chloro-1,4-dihydro-2,3-quinoxalinedione [ No CAS ]
  • 31
  • [ 123158-75-8 ]
  • 5-Iodo-7-chloro-6,8-dinitro-1,4-dihydro-2,3-quinoxalinedione [ No CAS ]
 

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Technical Information

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