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Chemical Structure| 78473-10-6 Chemical Structure| 78473-10-6

Structure of 78473-10-6

Chemical Structure| 78473-10-6

2-Aminopyridine-3,5-dicarbonitrile

CAS No.: 78473-10-6

4.5 *For Research Use Only !

Cat. No.: A123187 Purity: 97%

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Product Details of [ 78473-10-6 ]

CAS No. :78473-10-6
Formula : C7H4N4
M.W : 144.13
SMILES Code : N#CC1=CN=C(N)C(C#N)=C1
MDL No. :MFCD00462247
InChI Key :YLZXGBMEWRIPQX-UHFFFAOYSA-N
Pubchem ID :295912

Safety of [ 78473-10-6 ]

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

Computational Chemistry of [ 78473-10-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 38.07
TPSA ?

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

86.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.75
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

0.49
Log Po/w (WLOGP)?

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

0.42
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.

-1.02
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

0.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.24

Water Solubility

Log S (ESOL):?

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

-1.45
Solubility 5.16 mg/ml ; 0.0358 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.

-1.88
Solubility 1.92 mg/ml ; 0.0133 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

-1.81
Solubility 2.21 mg/ml ; 0.0153 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.

-6.83 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)

1.78

Application In Synthesis of [ 78473-10-6 ]

* 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 [ 78473-10-6 ]

[ 78473-10-6 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 51768-01-5 ]
  • [ 78473-10-6 ]
YieldReaction ConditionsOperation in experiment
73% EXAMPLE 3 2-Amino-3,5-dicyanopyridine (5) was prepared from 3 using the procedure described below for the preparation of 5 except that 5 was recrystallized from MeCN [methyl cyanide; acetonitrile) (instead of EtOH). The yield was 73% (7.00 g from 12.0 g (67.2 mmol) of 3] of product homogeneous on TLC (cyclohexane-EtOAc, 1:1); mp 220 C. dec; 1 H NMR (Me2 SO-d6) delta7.90 (s, NH2), 8.40 and 8.58 (two d, 4-H and 6H, J=2 Hz).
palladium; In 1,4-dioxane; Step A 2-amino-3.5-dicyanopyridine A mixture of 2-amino-6-chloro-3,5-dicyanopyridine (Synth. Comm. 1993, 2605, 15.0 g, 84 mmol) and 10% palladium on carbon (10.0 g) in dioxane (150 mL) was shaken on a Parr apparatus under hydrogen (55 psi) for 16 h. More catalyst (7.5 g) was added and after a further 4 h the reaction mixture was filtered through celite washing through with ethanol and evaporated in vacuo. The residue was partitioned between methylene chloride and 1 M HCl. The insoluble material was collected by filtration and dried to give the title compound. The methylene chloride layer was washed with brine, dried (Na2SO4) and evaporated in vacuo to give additional product: 1H NMR (DMSO) delta 7.93 (br s, 2H), 8.41 (d, J=2.2 Hz, 1H), 8.56 (d, J=2.2 Hz, 1H).
  • 2
  • [ 55244-11-6 ]
  • 3-Dimethylamino-2-formylacrylsaeurenitril [ No CAS ]
  • [ 78473-10-6 ]
  • 5
  • [ 78473-10-6 ]
  • [ 172208-08-1 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; sodium nitrite; In methanol; acetic acid; Step B 2-Chloro-3,5-dicyanopyridine Acetic acid (37 mL) was added over 10 min to sodium nitrite (13.4 g, 0.194 mol) with stirring. Concentrated sulfuric acid (12.3 mL) was added over 5 min to the resulting thick slurry which was then cooled to 0 C. In a separate flask, pyridinium hydrochloride (14.4 g, 0.125 mol) was added to a stirred mixture of <strong>[78473-10-6]2-amino-3,5-dicyanopyridine</strong> (4.0 g, 27.75 mmol) in acetic acid (55 mL) and the resulting mixture was cooled to 0 C. to give a thick slurry. The nitrite slurry was added to the aminopyridine slurry over 5 min with stirring at 0 C. Acetic acid (50 mL) was added and the thick slurry was warmed to rt. After 1 h at rt the mixture was warmed to 50 C. and after a further 1 h, it was poured into an ice/water mixture (500 mL). The aqueous mixture was extracted with methylene chloride (4 times) and the combined extracts were dried (Na2SO4) and evaporated to a yellow solid. The crude product was purified by chromatography on silica (chloroform/methanol gradient, 1-3% methanol) to give the title compound as a solid: 1H NMR (CDCl3) delta 8.34 (d, J=2.2 Hz, 1H), 8.88 (d, J=2.2 Hz, 1H).
With sulfuric acid; sodium nitrite; In methanol; acetic acid; Step B 2-Chloro-3,5-dicyanopyridine Acetic acid (37 mL) was added over 10 min to sodium nitrite (13.4 g, 0.194 mol) with stirring. Concentrated sulfuric acid (12.3 mL) was added over 5 min to the resulting thick slurry which was then cooled to 0 C. In a separate flask, pyridinium hydrochloride (14.4 g, 0.125 mol) was added to a stirred mixture of <strong>[78473-10-6]2-amino-3,5-dicyanopyridine</strong> (4.0 g, 27.75 mmol) in acetic acid (55 mL) and the resulting mixture was cooled to 0 C. to give a thick slurry. The nitrite slurry was added to the aminopyridine slurry over 5 min with stirring at 0 C. Acetic acid (50 mL) was added and the thick slurry was warmed to rt. After 1 h at rt the mixture was warmed to 50 C. and after a further 1 h, it was poured into an ice/water mixture (500 mL). The aqueous mixture was extracted with methylene chloride (4 times) and the. combined extracts were dried (Na2SO4) and evaporated to a yellow solid. The crude product was purified by chromatography on silica (chloroform/methanol gradient, 1-3% methanol) to give the title compound as a solid: 1H NMR (CDCl3) delta 8.34 (d, J=2.2 Hz, 1H), 8.88 (d, J=2.2 Hz, 1H).
  • 6
  • guanidine*HCl [ No CAS ]
  • Me2 SO (dimethyl sulfoxide) [ No CAS ]
  • NaOMe (sodium methoxide) [ No CAS ]
  • [ 78473-10-6 ]
  • [ 101810-72-4 ]
YieldReaction ConditionsOperation in experiment
In ethanol; EXAMPLE 5 2,4-Diaminopyrido[2,3-d]pyrimidine-6-carbonitrile (7). Guanidine*HCl (2.66 g, 27.8 mmol) was added to a solution of NaOMe (sodium methoxide) (1.50 g, 27.8 mmol) in absolute EtOH (180 mL). The mixture was stirred at 20-23 C. for 15 minutes before 5 (2.00 g, 13.9 mmol) was added. After a 24-hour reflux period with rapid stirring, TLC (cyclohexane-EtOAc, 1:1) showed absence of 5. The solid filtered from the cooled mixture was washed on the funnel with H2 O and EtOH; yield 95% (2.45 g). A sample of this material (1.0 g) was stirred with near-boiling Me2 SO (dimethyl sulfoxide) (250 mL), and the slightly cloudy solution was filtered (Celite) to give a clear, pale-yellow filtrate which was then concentrated by evaporation in vacuo (to about 60 mL). Addition of EtOH (200 mL) gave 7 as a light yellow solid (880 mg); 1 H NMR (Me2 SO-d6) delta6.97 (2, NH2), 7.84 (s, NH2), 8.87 and 8.91 (two d, 5-H and 7-H, J=2 Hz).
 

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