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Chemical Structure| 70416-53-4 Chemical Structure| 70416-53-4

Structure of 70416-53-4

Chemical Structure| 70416-53-4

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Product Details of [ 70416-53-4 ]

CAS No. :70416-53-4
Formula : C7H4N2O
M.W : 132.12
SMILES Code : O=CC1=CN=CC(=C1)C#N
MDL No. :MFCD07367908
InChI Key :RWPAJIVRGSWZAB-UHFFFAOYSA-N
Pubchem ID :12919806

Safety of [ 70416-53-4 ]

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

Computational Chemistry of [ 70416-53-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 34.34
TPSA ?

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

53.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.81
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

0.03
Log Po/w (WLOGP)?

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

0.77
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

1.46
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.44

Water Solubility

Log S (ESOL):?

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

-1.06
Solubility 11.6 mg/ml ; 0.0879 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.

-0.71
Solubility 25.7 mg/ml ; 0.194 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

-2.02
Solubility 1.25 mg/ml ; 0.00946 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.

-7.08 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

1.0 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)

1.34

Application In Synthesis of [ 70416-53-4 ]

* 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 [ 70416-53-4 ]

[ 70416-53-4 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 135124-71-9 ]
  • [ 70416-53-4 ]
YieldReaction ConditionsOperation in experiment
55% With manganese(IV) oxide; In dichloromethane; at 60℃; for 98h; d) 5-Cyano-pyridine-3-carbaldehyde A black suspension of <strong>[135124-71-9](5-cyano-pyridin-3-yl)-methanol</strong> (0.070 g, 0.52 mmol), anhydrous CH2Cl2 (1.04 mL) and manganese oxide (0.181 g, 2.09 mmol) was heated to reflux and monitored by TLC. After 8 h, the reaction mixture was cooled to room temperature and additional manganese oxide (0.095 g, 1.1 mmol) was added to the reaction flask. The reaction mixture was then heated to reflux. After 18 h, the reaction was still not complete by TLC and additional manganese oxide (0.097 g, 1.1 mmol) was added to the reaction flask. After heating at 60 C. for 72 h, the reaction mixture was cooled to room temperature, diluted with EtOAc (50 mL), passed through celite and washed with additional EtOAc (50 mL). The organic filtrate was dried over MgSO4, filtered through sintered glass and concentrated to yield 0.064 g (93%) of a white solid. It was purified by column chromatography (elution with EtOAC:hexanes, 1:3) and yielded 0.038 g (55%) of the title compound as a white solid. 1H NMR (CDCl3): 10.17 (s, 1H), 9.28 (d, J=1.9 Hz, 1H), 9.11 (d, J=2.2 Hz, 1H), 8.45 (dd, J=2.2, 1.9 Hz, 1H).
  • 2
  • [ 70416-53-4 ]
  • [ 135124-71-9 ]
YieldReaction ConditionsOperation in experiment
60.7% With sodium tetrahydroborate; In methanol; at 0℃; for 2.5h; To a stirred solution of 5formylnicotinonitrile (12 g, 91 mmol) in methanol (100 mL) at 0C, sodium borohydride (5.12 g, 136 mmol) was added portion wise for 30 minutes and stirred the mixture at 0C for 2 h. After TLC showed completion, the reaction mixture was concentrated and the residue was diluted with water (100 mL) and DCM (200 mL). The organic layer was dried over sodium sulfate and concentrated. The crude was purified by column chromatography (silicagel, 100- 200) using 1% MeOH in DCM to obtain 5-(hydroxymethyl)nicotinonitrile as yellow solid (Yield: 7.4 g, 60.7%). lH NMR (400 MHz, DMSO-d6): delta 4.50 (bs, 1H), 5.54 (s, 2H), 8.19 (s, 1H), 8.80 (s, 1H), 8.91 (s, 1H).
60.7% With methanol; sodium tetrahydroborate; at 0℃; for 2.5h; To a stirred solution of 5-formylnicotinonitrile (12 g, 0.091 mol) in methanol (100 mL) at 0C, sodium borohydride (5.12 g, 0.136 mol) was added portion wise for 30 minutes and stirred the mixture at 0C for 2 h. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and DCM (200 mL). The organic layer was dried over sodium sulfate and concentrated. The crude was purified by column chromatography (silica gel, 100-200 mesh) using 1% MeOH in DCM to obtain 5- (hydroxymethyl)nicotinonitrile as yellow solid (Yield: 7.4 g, 60.7%). 1 H NMR (400 MHz, DMSO-de, ppm): d, 8.91 (s, 1H), 8.80 (s, 1H), 8.19 (s, 1H), 5.54 (s, 2H), 4.50 (bs, 1H).
 

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Technical Information

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