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Chemical Structure| 60323-96-8 Chemical Structure| 60323-96-8

Structure of 60323-96-8

Chemical Structure| 60323-96-8

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Product Details of [ 60323-96-8 ]

CAS No. :60323-96-8
Formula : C6H5ClN2O3
M.W : 188.57
SMILES Code : O=[N+](C1=C(C)C=[N+]([O-])C(Cl)=C1)[O-]
MDL No. :MFCD09880009
InChI Key :DXJQKWNJVPTPSK-UHFFFAOYSA-N
Pubchem ID :12318010

Safety of [ 60323-96-8 ]

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

Computational Chemistry of [ 60323-96-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 46.4
TPSA ?

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

71.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.53
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

1.01
Log Po/w (WLOGP)?

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

1.19
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.

1.28
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

-0.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.61

Water Solubility

Log S (ESOL):?

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

-1.95
Solubility 2.12 mg/ml ; 0.0112 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-2.1
Solubility 1.51 mg/ml ; 0.00801 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

-1.01
Solubility 18.2 mg/ml ; 0.0966 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

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

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.

-6.73 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

5.0 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)

2.21

Application In Synthesis of [ 60323-96-8 ]

* 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 [ 60323-96-8 ]

[ 60323-96-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 60323-96-8 ]
  • [ 79055-62-2 ]
YieldReaction ConditionsOperation in experiment
77.63% With hydrogenchloride; iron; In ethanol; at 60 - 65℃; for 0.5h; In a flask, 107 mL of 80% ethanol and 30 g of the product of Step 2, The temperature was raised to 60 C, HCl was added, and Fe powder was added in batches. The temperature was controlled at 60-65 C. After the addition, the reaction was carried out for about 30 min, and the reaction was monitored by TLC under the following conditions: EpsilonAlpha:CH2Cl2 = 1:5. After the reaction, the solution was cooled to room temperature, adjusted to pH 8 with NaOH solution, and then filtered and dried. With 4 times the volume of dichloromethane temperature reflux dissolved to clarify, down to room temperature, adding petroleum ether in 17 g white product, the yield was 77.63%.
With iron; acetic acid; at 100℃; for 0.333333h; Iron (1.0 g) was added to a solution of 2-chloro-5-methyl-4-nitropyridine N-oxide (500 mg, 2.6 mmol) in glacial acetic acid (10 mL). The reaction mixture was then heated at 100 C for 20 minutes. The suspension was poured onto aqueous NaOH (1M) and extracted with ethyl acetate. After drying over Na2S04, the solvent was then evaporated and the title compound was isolated as a colorless solid (370 mg, 2.6 mmol, HPLC Rt 1.3 min, FIA ES+ 143.0).
With iron; acetic acid; at 100℃; for 0.333333h; 4-Amino-2-chloro-5-methylpyridine (11) : Iron (1. 0 g) was added to a solution of 10 (500 mg, 2.6 mmol) in glacial acetic acid (10 mL). The reaction mixture was then heated at 100 C for 20 minutes. The suspension was poured on aqueous NaOH 1M and extracted with ethyl acetate. After drying over Na2SO4, the solvent was then evaporated and 11 was isolated as a colorless solid (370 mg, 2.6 mmol, HPLC Rt 1.3 min, FIA ES+ 143.0).
With iron; acetic acid; In tetrahydrofuran; methanol; at 30 - 80℃; for 0.666667h; To a mixture of 2-chloro-5-methyl-4-nitropyridine 1 -oxide (50 g, 265 mmol) in acetic acid (200 mL) was added iron (74.0 g, 1326 mmol) at 30 C. The solution was stirred at 80 C for 40 min. The mixture was poured into aq. NaOH (1M, 4000 mL) and extracted with EtOAc (1000 mL x 3). The combined organic layers were washed with brine (800 mL), dried over anhydrous Na2S04 and filtered. The filtrate was concentrated in vacuum to give 2-chloro-5- methylpyridin-4-amine as a light yellow oil, which was used directly without further purification. MS: 143 (M + 1). 1H MR (400 MHz, d4-methanol) delta 7.65 (s, 1H), 6.55 (s, 1H), 2.03 (s, 3H).

 

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Technical Information

Categories

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