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Chemical Structure| 5344-44-5 Chemical Structure| 5344-44-5

Structure of 5344-44-5

Chemical Structure| 5344-44-5

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Product Details of [ 5344-44-5 ]

CAS No. :5344-44-5
Formula : C6H5ClN2O2
M.W : 172.57
SMILES Code : NC1=CC(Cl)=CC(=C1)[N+]([O-])=O
MDL No. :MFCD01009865
InChI Key :RXAFMJXGEACRGX-UHFFFAOYSA-N
Pubchem ID :219615

Safety of [ 5344-44-5 ]

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

Computational Chemistry of [ 5344-44-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
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 44.68
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.

1.07
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

1.78
Log Po/w (WLOGP)?

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

1.84
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.

0.88
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

-0.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.04

Water Solubility

Log S (ESOL):?

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

-2.37
Solubility 0.738 mg/ml ; 0.00428 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.

-2.91
Solubility 0.214 mg/ml ; 0.00124 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

-2.03
Solubility 1.61 mg/ml ; 0.00931 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

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.

-6.09 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<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)

2.15

Application In Synthesis of [ 5344-44-5 ]

* 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.

  • Upstream synthesis route of [ 5344-44-5 ]
  • Downstream synthetic route of [ 5344-44-5 ]

[ 5344-44-5 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 618-86-0 ]
  • [ 5344-44-5 ]
YieldReaction ConditionsOperation in experiment
84% With diammonium sulfide In ethanol; water for 1 h; Heating / reflux The above product (0.50 g, 2.47 mmol) was refluxed 1 hr in 6 mL alcohol and 3 mL 20percent ammonium sulfide in H2O. Water was added and the product was filtered, dried and flash chromatographed on silica gel eluting with 10percent acetone-pet ether to obtain 3-chloro-5-nitroaniline (0.36 g, 84percent) as an orange powder.
53% With diammonium sulfide In ethanol; water at 80℃; for 1 h; Example 883-Chloro-5-nitroaniline1-Chloro-3,5-dinitrobenzene (512 mg, 2.5 mmol) was dissolved into EtOH (8 ml) with the aid of sonication. (NH4)2S (3 ml, 20percent in H2O) was added to the solution and heated at 80° C. for 1 hour, followed by thin layer chromatography (3:1 Hexanes:Ethyl Acetate). After the completion of reaction, the solution was allowed to cool to room temperature, ethyl acetate (75 ml) was added and washed with brine (30 ml). The 2 layers were separated, the organic layer was dried with Na2SO4 and concentrated under reduced pressure after filtering off solid. The title compound (225 mg, 53percent yield) was obtained by purifying the residue with flash column chromatography (3:1 Hexanes:Ethyl Acetate) as an orange solid.1H NMR (300 MHz, DMSO) δ 7.32 (s, 1H), 7.24 (s, 1H), 6.94 (s, 1H), 6.14 (s, 2H); LCMS (m/z): 173.04 (MH+).
28% With diammonium sulfide; water In ethanol at 80℃; for 1 h; To a stirred solution of 1-chloro-3,5-dinitrobenzene 8 (3.80 g, 19 mmol) in ethanol (60 mL) was added ammonium sulfide (20percent aqueous solution, 20 mL) and the mixture was heated at 80°C for lh. The mixture was then partitioned between water and ethyl acetate, the ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and solvents evaporated to obtain a crude material, purification of which by flash chromatography on silica gel (using 40 g SNAP column and 30percent ethyl acetate in hexane as eluent) afforded 3-chloro-5-nitroaniline precursor-Olin 28percent yield as orange colored solid. MS: 171.02 (M+H).
References: [1] Patent: US6353013, 2002, B1, . Location in patent: Page column 28.
[2] Patent: US2011/130415, 2011, A1, . Location in patent: Page/Page column 65.
[3] Patent: WO2015/25197, 2015, A1, . Location in patent: Paragraph 00070.
[4] Journal of the Chemical Society, 1905, vol. 87, p. 1265.
[5] Bulletin de la Societe Chimique de France, 1938, vol. &lt;5&gt; 5, p. 1441,1444[6] Anales de la Asociacion Quimica Argentina (1921-2001), 1938, vol. 26, p. 41,44, 45.
[7] Journal of Organic Chemistry, 1975, vol. 40, # 20, p. 2906 - 2910.
[8] Journal of Organic Chemistry, 1977, vol. 42, # 1, p. 166 - 169.
[9] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1974, p. 1860 - 1862.
[10] Angewandte Chemie - International Edition, 2009, vol. 48, # 50, p. 9538 - 9541.
[11] Journal of Agricultural and Food Chemistry, 2016, vol. 64, # 18, p. 3697 - 3704.
  • 2
  • [ 618-87-1 ]
  • [ 5344-44-5 ]
References: [1] Bulletin de la Societe Chimique de France, 1938, vol. &lt;5&gt; 5, p. 1441,1444[2] Anales de la Asociacion Quimica Argentina (1921-2001), 1938, vol. 26, p. 41,44, 45.
[3] Journal of Organic Chemistry, 1975, vol. 40, # 20, p. 2906 - 2910.
[4] Journal of Organic Chemistry, 1977, vol. 42, # 1, p. 166 - 169.
[5] Patent: US2011/130415, 2011, A1, .
[6] Patent: WO2015/25197, 2015, A1, .
  • 3
  • [ 99-65-0 ]
  • [ 5344-44-5 ]
References: [1] Journal of Agricultural and Food Chemistry, 2016, vol. 64, # 18, p. 3697 - 3704.
 

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