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Structure of 95-11-4

Chemical Structure| 95-11-4

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Product Details of [ 95-11-4 ]

CAS No. :95-11-4
Formula : C8H9N
M.W : 119.16
SMILES Code : N#CC1C(C2)C=CC2C1
MDL No. :MFCD00167563
InChI Key :BMAXQTDMWYDIJX-UHFFFAOYSA-N
Pubchem ID :7218

Safety of [ 95-11-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H227
Precautionary Statements:P501-P261-P270-P210-P271-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312-P403+P235

Computational Chemistry of [ 95-11-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.62
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 35.62
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.74
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

1.36
Log Po/w (WLOGP)?

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

1.72
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.

1.58
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

1.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.56

Water Solubility

Log S (ESOL):?

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

-1.44
Solubility 4.37 mg/ml ; 0.0367 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.

-1.46
Solubility 4.11 mg/ml ; 0.0345 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

-0.69
Solubility 24.1 mg/ml ; 0.202 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.

-6.06 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

2.0
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)

4.46

Application In Synthesis of [ 95-11-4 ]

* 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.

  • Upstream synthesis route of [ 95-11-4 ]

[ 95-11-4 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 67403-76-3 ]
  • [ 121-46-0 ]
  • [ 2436-90-0 ]
  • [ 95-11-4 ]
YieldReaction ConditionsOperation in experiment
71% With bis(1,5-cyclooctadiene)nickel (0); dimethylaluminum chloride; bis[2-(diphenylphosphino)phenyl] ether In hexane; benzene at 28℃; for 16 h; Inert atmosphere; Glovebox 69 (82.6 mg, 0.50 mmol), norbornadiene 8 (51 μΙ_, 0.5 mmol) and 1 .0M solution of AIMe2CI in hexane (50 μΙ_, 10.0 molpercent, 0.05 mmol) were added sequentially to a solution of Ni(COD)2 (3.45 mg, 2.5 molpercent, 12.5 μηηοΙ) and DPEphos (6.75 mg, 2.5 ηηο /ο , 12.5 μιτιοΙ) in benzene (1 .0 ml_) prepared in a 4 ml_ Screw-cap vial under an argon atmosphere in a glove box. The vial was taken out of the glove box, the temperature of which was fixed at 28 °C. The reaction mixture was stirred for 16 hours at 28 °C. After that time, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (100percent pentane) to 70 (49.0 mg, yield: 71 percent). 1H NMR (500 MHz, CDCI3) δ 5.74 - 5.64 (m, 1 H), 5.13 - 5.06 (m, 1 H), 4.99 - 4.88 (m, 2H), 2.12 (p, J = 7.0 Hz, 1 H), 2.01 - 1 .89 (m, 2H), 1 .68 (s, 3H), 1 .60 (s, 3H), 1 .35 - 1 .26 (m, 2H), 0.99 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCI3) δ 144.91 , 131 .44, 124.80, 1 12.61 , 37.51 , 36.89, 25.88, 20.30, 17.83
References: [1] Patent: WO2017/93149, 2017, A1, . Location in patent: Page/Page column 28.
  • 2
  • [ 5453-80-5 ]
  • [ 95-11-4 ]
YieldReaction ConditionsOperation in experiment
92% With bismuth(lll) trifluoromethanesulfonate; acetylhydroxamic acid In acetonitrile for 15 h; Reflux General procedure: 4-Isopropylbenzaldehyde 1a (0.50 g, 3.37 mmol), acetohydroxamic acid (0.30 g, 4.05 mmol), acetonitrile (5 ml), and Bi(OTf)3 (0.11 g, 0.17 mmol) were taken into a 25 ml round-bottomed flask fitted with a condenser and calcium chloride guard tube. The mixture was refluxed for 14 h and after completion of the reaction (GC, 10percent SE-30 on Chromosorb, 10' .x. 1/8 column), the reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude product obtained was purified by normal column chromatography(silica gel 100-200 mesh, ethyl acetate/hexane = 1:20) to obtain 4-isopropylbenzonitrile 3a (0.47 g, 97percent).
References: [1] Tetrahedron Letters, 2012, vol. 53, # 27, p. 3421 - 3424.
  • 3
  • [ 542-92-7 ]
  • [ 107-13-1 ]
  • [ 95-11-4 ]
YieldReaction ConditionsOperation in experiment
80.8% at 40 - 50℃; for 1.75 h; Example 1:; Preparation of 5-Cyanonorbornene:; To a solution of acrylonitrile (249.4 g, 4.7 mol) in methanol (260 mL) at 40° C was added cyclopentadiene monomer (311.0 g, 4.7 mol) slowly over a period of 45 <n="5"/>min. The temperature of the reaction was maintained between 40 and 50 C for one hour. The solvent was removed under vacuum to obtain a residue (487.3 g), which on distillation under high vacuum produced 5-cyanonorbornene (453.3 g, 80.8percent yield).
300.7 g at 160 - 180℃; for 7 h; Autoclave Acrylonitrile (163.6 g, 3.08 mol) to which dicyclopentadiene having a purity of 95percent (195.0g, 1.40 mol) and N-nitrosodiphenylamine(0.36 g, 1.8 mmol) were added was added into a 1000 ml autoclave, reacted under stirring at 160°C for 5 hours, then, further heated, and reacted at 180°C for 2 hours. A reaction liquid including an obtained bicyclo[2.2.1]-5-heptene-2-carbonitrile weighed 355.6 g, and an analysis showed that 331.2 g (2.78 mol) of bicyclo[2.2.1]-5-heptene-2-carbonitrile was included. 352.4 g of the reaction liquid including 328.2 g (2.75 mol) of the obtained bicyclo[2.2.1]-5-heptene-2-carbonitrile was added into a 500 ml flask, and distilled under reduced pressure, thereby obtainingbicyclo[2.2.1]-5-heptene-2-carbonitrile (300.7 g, 2.52 mol) as a principle distillate.
References: [1] Journal of the Chemical Society - Series Chemical Communications, 1991, # 18, p. 1279 - 1281.
[2] Journal of the Chinese Chemical Society, 2004, vol. 51, # 2, p. 367 - 370.
[3] Tetrahedron Letters, 2004, vol. 45, # 25, p. 4943 - 4946.
[4] Patent: WO2008/65672, 2008, A2, . Location in patent: Page/Page column 3-4.
[5] Journal of the American Chemical Society, 1994, vol. 116, # 26, p. 12115 - 12116.
[6] European Journal of Inorganic Chemistry, 2005, # 4, p. 676 - 684.
[7] Tetrahedron, 2005, vol. 61, # 30, p. 7105 - 7111.
[8] Journal of the American Chemical Society, 1980, vol. 102, # 26, p. 7816 - 7817.
[9] Journal of Organic Chemistry USSR (English Translation), 1992, vol. 28, # 11.1, p. 1806 - 1813[10] Zhurnal Organicheskoi Khimii, 1992, vol. 28, # 11, p. 2244 - 2252.
[11] Tetrahedron, 1998, vol. 54, # 11, p. 2631 - 2646.
[12] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1989, p. 1223 - 1228.
[13] Synlett, 1997, vol. 1997, # 7, p. 786 - 788.
[14] Synlett, 1997, vol. 1997, # 7, p. 786 - 788.
[15] Patent: EP2708527, 2014, A1, . Location in patent: Paragraph 0088.
  • 4
  • [ 77-73-6 ]
  • [ 107-13-1 ]
  • [ 95-11-4 ]
YieldReaction ConditionsOperation in experiment
355.6 g at 160 - 180℃; for 7 h; Autoclave Synthesis of bicyclo[2.2.1]-5-heptene-2-carbonitrile
195.0 g (1.40 mol) of dicyclopentadiene having purity of 95percent and 163.6 (3.08 mol) of acrylonitrile to which 0.36 g (1.8 mmol) of N-nitrosodiphenylamine was added were put into a 1,000 ml autoclave.
The components were reacted for 5 hours at 160° C. while being stirred and then heated to 180° C. and reacted for 2 hours, and the reaction ended.
In this way, 355.6 g of a reaction liquid containing bicyclo[2.2.1]-5-heptene-2-carbonitrile was obtained.
References: [1] Patent: EP2918576, 2015, A1, . Location in patent: Paragraph 0076.
[2] Patent: US2015/291513, 2015, A1, . Location in patent: Paragraph 0139.
  • 5
  • [ 90086-80-9 ]
  • [ 95-11-4 ]
References: [1] Synthetic Communications, 2008, vol. 38, # 21, p. 3810 - 3815.
 

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