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Chemical Structure| 38203-08-6

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Product Details of [ 38203-08-6 ]

CAS No. :38203-08-6
Formula : C8H8N2
M.W : 132.16
SMILES Code : N#CCC1=NC=C(C)C=C1
MDL No. :MFCD09923761
InChI Key :SFVRNNBFZQKRAQ-UHFFFAOYSA-N
Pubchem ID :583430

Safety of [ 38203-08-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Computational Chemistry of [ 38203-08-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.73
TPSA ?

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

36.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.51
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

0.91
Log Po/w (WLOGP)?

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

1.46
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.

0.46
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

2.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

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

-1.61
Solubility 3.24 mg/ml ; 0.0245 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.

-1.27
Solubility 7.17 mg/ml ; 0.0542 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

-2.87
Solubility 0.179 mg/ml ; 0.00136 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.

-6.46 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)

1.38

Application In Synthesis of [ 38203-08-6 ]

* 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.

  • Upstream synthesis route of [ 38203-08-6 ]

[ 38203-08-6 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 2369-19-9 ]
  • [ 75-05-8 ]
  • [ 38203-08-6 ]
YieldReaction ConditionsOperation in experiment
53%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.916667 h;
Stage #2: at -78 - 20℃; for 2 h;
General procedure: To a solution of n-butyllithiun (21.0 mL, 33.6 mmol, 1.6mol/L) in THF (75 mL) was slowly added acetonitrile(1.75 mL, 33.5 mmol) for 10 min at -78°C,and then the mixture was stirred at this temperature for 45 min. To the mixturewas added a solution of 2-halo-pyridine (15.0 mmol) in THF (25 mL) at -78°C, and then the mixture was stirred at thistemperature for 2 h, and then gradually heated until room temperature. Afterthe addition of saturated aqueous solution of ammonium chloride, the mixturewas extracted with ethyl acetate, and then washed with brine and dried over Na2SO4.The mixture was concentrated in vacuo. Thecrude material waspurified by flash column chromatography on a silica gel(Hexane:AcOEt) togive 5d, 5e, and 5h.
1.05 g
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.916667 h; Inert atmosphere
Stage #2: at -78℃; for 2 h; Inert atmosphere
5-Methyl-2-pyridineacetonitrile [0445] n-Butyllithium (21.0 mL, a 1.6 mol/L n-hexane solution) was diluted with tetrahydrofuran (75 mL) under an argon atmosphere, then acetonitrile (1.75 mL) was added at -78°C over 10 minutes, and then the mixture was stirred at -78°C for 45 minutes. A tetrahydrofuran (25 mL) solution of 2-fluoro-5-methylpyridine (1.67 g) was added to the reaction mixture, then the reaction mixture was stirred at -78°C for 2 hours, and then it was gradually heated up to room temperature. A saturated ammonium chloride aqueous solution was added to the reaction mixture and then the mixture was extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue thus obtained was purified by silica gel chromatography (ethyl acetate:n-hexane = 1:1) to obtain a title compound as a colorless crystal (1.05 g). 1H-NMR (400 MHz, CDCl3) δ 2.05 (3H, s), 3.90 (2H, s), 7.32 (1H, d, J = 7.9 Hz), 7.54 (1H, dd, J = 7.9,1.8 Hz), 8.40 (1H, d, J =1.8 Hz)
References: [1] Tetrahedron Letters, 2014, vol. 55, # 43, p. 5963 - 5966.
[2] Patent: EP2669285, 2013, A1, . Location in patent: Paragraph 0444; 0445.
  • 2
  • [ 3510-66-5 ]
  • [ 38203-08-6 ]
YieldReaction ConditionsOperation in experiment
80% With n-butyllithium In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; hexane; acetonitrile Step 3-Preparation of 2-(5-methylpyridin-2-yl)acetonitrile
To a solution of anhydrous acetonitrile (10.1 mL, 191.83 mmol, 3.3 equiv.) in dry THF (500 mL) was added dropwise n-butyl lithium (2.5 M in hexane, 69.8 mL, 174.39 mmol, 3 equiv.) at minus 78° C. under nitrogen atmosphere.
The resulting white suspension was stirred at minus 78° C. for 1 hour, and then a solution of 2-bromo-5-methylpyridine (10.0 g, 58.13 mmol, 1 equiv.) in dry THF (30 mL) was added.
The reaction mixture was kept at minus 78° C. for 1 hour and then warmed up slowly to room temperature and stirred for another hour.
Ice water was added and the layer was separated.
The organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated to give 18 g of crude product.
The crude product was purified by silica-gel column chromatography (eluent, PE/EtOAc=15:1) to give 2-(5-methylpyridin-2-yl)acetonitrile (6.2 g, yield 80percent).
1H NMR (300 MHz, CDCl3): δ 8.40 (d, J=3.0 Hz, 1H), 7.54 (dd, J1=3.0 Hz, J2=6.0 Hz, 1H), 7.32 (d, J=6.0 Hz, 1H), 3.90 (s, 2H), 2.40 (s, 3H).
References: [1] Patent: US2009/280230, 2009, A1, .
[2] Patent: US2009/280230, 2009, A1, .
[3] Patent: US2009/280230, 2009, A1, .
  • 3
  • [ 3510-66-5 ]
  • [ 75-05-8 ]
  • [ 38203-08-6 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 2 h;
To a solution of anhydrous acetonitrile (10.1 mL, 191.83 mmol, 3.3 equiv.) in dry THF (500 mL) was added dropwise n-butyl lithium (2.5 M in hexane, 69.8 mL, 174.39 mmol, 3 equiv.) at minus 78° C. under nitrogen atmosphere. The resulting white suspension was stirred at minus 78° C. for 1 hour, and then a solution of 2-bromo-5-methylpyridine (10.0 g, 58.13 mmol, 1 equiv.) in dry THF (30 mL) was added. The reaction mixture was kept at minus 78° C. for 1 hour and then warmed up slowly to room temperature and stirred for another hour. Ice water was added and the layer was separated. The organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated to give 18 g of crude product. The crude product was purified by silica-gel column chromatography (eluent, PE/EtOAc=15:1) to give 2-(5-methylpyridin-2-yl)acetonitrile (6.2 g, yield 80percent). 1H NMR (300 MHz, CDCl3): δ 8.40 (d, J=3.0 Hz, 1H), 7.54 (dd, J1=3.0 Hz, J2=6.0 Hz, 1H), 7.32 (d, J=6.0 Hz, 1H), 3.90 (s, 2H), 2.40 (s, 3H).
References: [1] Patent: US8148536, 2012, B2, . Location in patent: Page/Page column 79.
[2] Patent: US8148536, 2012, B2, . Location in patent: Page/Page column 73.
  • 4
  • [ 22940-71-2 ]
  • [ 38203-08-6 ]
References: [1] Yakugaku Zasshi, 1959, vol. 79, p. 108[2] Chem.Abstr., 1959, p. 10211.
  • 5
  • [ 772-71-4 ]
  • [ 38203-08-6 ]
References: [1] Yakugaku Zasshi, 1959, vol. 79, p. 108[2] Chem.Abstr., 1959, p. 10211.
  • 6
  • [ 767-01-1 ]
  • [ 151-50-8 ]
  • [ 38203-08-6 ]
References: [1] Yakugaku Zasshi, 1959, vol. 79, p. 108[2] Chem.Abstr., 1959, p. 10211.
 

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