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Chemical Structure| 55557-52-3 Chemical Structure| 55557-52-3

Structure of 55557-52-3

Chemical Structure| 55557-52-3

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CAS No.: 55557-52-3

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Product Details of [ 55557-52-3 ]

CAS No. :55557-52-3
Formula : C5H2ClN3
M.W : 139.54
SMILES Code : C1=CN=C(C(=N1)C#N)Cl
MDL No. :MFCD00219653
InChI Key :SDLFAEGTVBPHBK-UHFFFAOYSA-N
Pubchem ID :292465

Safety of [ 55557-52-3 ]

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

Computational Chemistry of [ 55557-52-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 31.76
TPSA ?

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

49.57 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

1.29
Log Po/w (WLOGP)?

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

1.0
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.

-0.84
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

1.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.81

Water Solubility

Log S (ESOL):?

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

-2.01
Solubility 1.36 mg/ml ; 0.00975 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.

-1.93
Solubility 1.64 mg/ml ; 0.0117 mol/l
Class?

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

Very 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

-2.33
Solubility 0.657 mg/ml ; 0.00471 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.

-6.24 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

0.0 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)

1.97

Application In Synthesis of [ 55557-52-3 ]

* 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 [ 55557-52-3 ]
  • Downstream synthetic route of [ 55557-52-3 ]

[ 55557-52-3 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 55557-52-3 ]
  • [ 21279-62-9 ]
YieldReaction ConditionsOperation in experiment
80% With dihydrogen peroxide; sodium hydroxide In water at 50 - 60℃; for 2.5 h; The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 °C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 °C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34,42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 °C. The pH was adjusted and regulated around a value of 9 using an 8percent solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 °C. The reaction was stopped after 2.5 h and was cooled to 5 °C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].
80% at 50 - 55℃; for 3 h; The starting compound 3-chloropyrazine-2-carboxamide was prepared via partial hydrolysis of the nitrile group of 3-chloropyrazine-2-carbonitrile (Fluorochem, Co., Hadfield, Derbyshire, UK). A mixture of concentrated (30percent) hydrogen peroxide (29 mL) and water (195 mL) was prepared and alkalinized with an 8percent (w/v) solution of sodium hydroxide to obtain a solution with pH 9. The carbonitrile (104 mmol) was then added portionwise into the heated (50 °C) mixture over a period of 30 min. The whole mass was stirred for an additional 2.5 h at 55 °C while the pH was periodically monitored and alternatively adjusted to the value of 9 by adding a few drops of 8percent NaOH solution. The reaction mixture was cooled in a fridge to initiate crystallization. The crude product was recrystallized from ethanol [27]. The yield of this reaction was approximately 80percent.
References: [1] Molecules, 2014, vol. 19, # 7, p. 9318 - 9338.
[2] Molecules, 2017, vol. 22, # 2, .
 

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Technical Information

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