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Chemical Structure| 58481-14-4 Chemical Structure| 58481-14-4
Chemical Structure| 58481-14-4

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Ethyl 2-cyanoisonicotinate

CAS No.: 58481-14-4

4.5 *For Research Use Only !

Cat. No.: A193700 Purity: 97%

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Product Details of [ 58481-14-4 ]

CAS No. :58481-14-4
Formula : C9H8N2O2
M.W : 176.17
SMILES Code : O=C(OCC)C1=CC=NC(C#N)=C1
MDL No. :MFCD10574965
InChI Key :HZIKYLAZZZSYKF-UHFFFAOYSA-N
Pubchem ID :13415157

Safety of [ 58481-14-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Calculated chemistry of [ 58481-14-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 45.04
TPSA ?

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

62.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.83
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

1.12
Log Po/w (WLOGP)?

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

1.13
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.

0.04
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

1.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.13

Water Solubility

Log S (ESOL):?

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

-1.78
Solubility 2.91 mg/ml ; 0.0165 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.

-2.04
Solubility 1.62 mg/ml ; 0.0092 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

-2.59
Solubility 0.454 mg/ml ; 0.00258 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

Yes
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.

-6.58 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)

1.96

Application In Synthesis [ 58481-14-4 ]

* 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 [ 58481-14-4 ]

[ 58481-14-4 ] Synthesis Path-Downstream   1~26

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  • 2-(5-{(1R)-4-CYCLOHEXYL-1-[2-(HYDROXYAMINO)-2-OXOETHYL]BUTYL}-1,2,4-OXADIAZOL-3-YL)ISONICOTINAMIDE [ No CAS ]
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  • C21H29N5O4 [ No CAS ]
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  • [ 468068-18-0 ]
  • 13
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  • 2-(5-{(1R)-4-CYCLOHEXYL-1-[2-(HYDROXYAMINO)-2-OXOETHYL]BUTYL}-1,2,4-OXADIAZOL-3-YL)-N,N-DIMETHYLISONICOTINAMIDE [ No CAS ]
  • 14
  • [ 58481-14-4 ]
  • C26H39N3O6 [ No CAS ]
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  • 2-(5-{(1R)-4-CYCLOHEXYL-1-[2-(HYDROXYAMINO)-2-OXOETHYL]BUTYL}-1,2,4-OXADIAZOL-3-YL)ISONICOTINIC ACID [ No CAS ]
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  • [ 58481-03-1 ]
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  • [ 103851-93-0 ]
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  • [ 24424-99-5 ]
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  • [ 473924-62-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; triethylamine;palladium; In ethanol; dichloromethane; toluene; Preparation 112 Ethyl 2-[(tert-butoxycarbonyl)amino]methyl}isonicotinate To a stirred solution of <strong>[58481-14-4]ethyl 2-cyanoisonicotinate</strong> (2.00 g, 110 mmol, J. Med. Chem., 1976,19, 483) in ethanol (20 ml) was added 2M aqueous hydrochloric acid solution (7.5 ml) followed by 5% palladium on carbon (200 mg). The reaction mixture was stirred at room temperature under a hydrogen atmosphere (60 psi) for 48 hours. The mixture was filtered through arbocel and the filtrate was concentrated under reduced pressure. The residue was dried by azeotropic distillation using toluene under reduced pressure. To a stirred solution of the residue (3.00 g) in dichloromethane (22 ml) was added triethylamine (4.6 ml, 33 mmol) followed by di-tert-butyl dicarbonate (2.62 g, 12.0 mmol). After stirring for 1 hour at room temperature the reaction mixture was diluted with dichloromethane (100 ml) and washed with water (50 ml). The organic component was washed with brine (50 ml), dried over magnesium sulphate and concentrated under reduced pressure to give a brown oily solid. The crude product mixture was purified by flash chromatography on silica gel eluding with dichloromethane:methanol:0.88 ammonia (98:2:0.2 then 97:3:0.3, by volume) to provide the title compound (2.20 g) as a yellow oil. 1H NMR (400 MHz, CDCl3): delta=1.38 (t, 3H), 1.45 (s, 9H), 4.38 (q, 2H), 4.50 (m, 2H), 5.50 (broad s, 1H), 7.73 (d, 1H), 7.81 (s, 1H), 8.65 (d, 1H). LRMS (electrospray): m/z 281 (MH+)
  • 25
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  • [ 468067-78-9 ]
  • [ 468068-11-3 ]
YieldReaction ConditionsOperation in experiment
Preparation 39 Ethyl 2-[amino(hydroxyimino)methyl]isonicotinate The title compound was obtained as a pale yellow solid from <strong>[58481-14-4]ethyl-2-cyanoisonicotinate</strong> (Heterocycles 1987, 26, 73 1) using a similar method to that described in Preparation 4. 1H NMR (400 MHz, D6-DMSO) delta 1.28 (t, 3H), 4.34 (q, 2H), 5.87 (s, 2H), 7.78 (d, 1H), 8.25 (s, 1H), 8.70 (d, 1H), 10.03 (s, 1H). LRMS (ES) 210 (M+H).
  • 26
  • [ 557-21-1 ]
  • [ 14906-37-7 ]
  • [ 58481-14-4 ]
YieldReaction ConditionsOperation in experiment
85% With N,N-Dimethylcarbamoyl chloride; In toluene; for 2.0h;Reflux; Inert atmosphere; A reaction mixture of 4-(ethoxycarbonyl)pyridine-1-oxide28 (3.64 g, 21.82 mmol), DMCC (3.01 mL, 32.73 mmol) and Zn(CN)2(3.84 g, 32.73 mmol) in toluene (40 mL) was heated under reflux under an argon atmosphere for 2 h. The reaction mixture was cooled to room temperature and H2O (30 mL) was added, and stirring was continued for 15 min. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure to yield a brown solid. This was then passed through a silica plug using EtOAc:Pet. Ether in a 2:1 ratio as the eluent yielding a yellow oil which solidified on ice. Orange solid (3.28 g, 85%). m.p. 39-40 C (lit. 42-44 C);14 numax (KBr) 2988, 2964, 2238, 1728, 1597, 1557, 1470, 1402, 1393, 1370, 1298, 1281, 1202, 1113, 1015, 990, 918, 890, 862, 763, 686 cm-1; deltaH (300 MHz, CDCl3) 8.90 (1 H, dd, J 4.9, 0.9 Hz, pyr-H), 8.25 (1 H, dd, J 1.5, 0.9 Hz, pyr-H), 8.10 (1 H, dd, J 4.9, 1.5 Hz, pyr-H), 4.47 (2 H, q, J 7.1 Hz, OCH2), 1.44 (3 H, t, J 7.1 Hz, CH3); deltaC (75 MHz, CDCl3) 163.1 (C=O), 151.9, 139.0, 134.7, 127.6, 126.1, 116.6 (CN), 62.6 (OCH2), 14.1 (CH3); HRMS (ESI): [M+H]+, found 177.0659. C9H9N2O2 requires 177.0659. NMR data is in agreement with literature data.14
 

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Technical Information

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