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Chemical Structure| 960370-97-2 Chemical Structure| 960370-97-2

Structure of 960370-97-2

Chemical Structure| 960370-97-2

1-Cyclopropyl-4-oxocyclohexanecarbonitrile

CAS No.: 960370-97-2

4.5 *For Research Use Only !

Cat. No.: A114088 Purity: 95%

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Product Details of [ 960370-97-2 ]

CAS No. :960370-97-2
Formula : C10H13NO
M.W : 163.22
SMILES Code : N#CC1(C2CC2)CCC(CC1)=O
MDL No. :MFCD17013941
InChI Key :PHPMGMPLWGFZKK-UHFFFAOYSA-N
Pubchem ID :53407212

Safety of [ 960370-97-2 ]

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

Computational Chemistry of [ 960370-97-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 45.64
TPSA ?

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

40.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.56
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

1.06
Log Po/w (WLOGP)?

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

1.99
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.

1.27
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

2.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.7

Water Solubility

Log S (ESOL):?

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

-1.45
Solubility 5.74 mg/ml ; 0.0352 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.

-1.51
Solubility 5.05 mg/ml ; 0.031 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

-2.1
Solubility 1.3 mg/ml ; 0.00794 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.

-6.54 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)

1.85

Application In Synthesis of [ 960370-97-2 ]

* 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 [ 960370-97-2 ]

[ 960370-97-2 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 960370-95-0 ]
  • [ 960370-97-2 ]
YieldReaction ConditionsOperation in experiment
92.8% With trifluoroacetic acid; In dichloromethane; at 0℃; The solution of the compound represented by the formula 3 (8-cyclopropyl-1,4-dioxaspiro [4.5] decane-8-carbonitrile) in dichloromethane is contacted with the compound represented by the formula Dichloromethane solution was added trifluoroacetic acid, stirring to the thin layer chromatography without raw materials,And the molar ratio of the compound represented by the formula 3 to trifluoroacetic acid is 0.5: 1,The reaction temperature of the reaction system is 0 C,At 0 ,To a solution of compound 3 (103.5 g, 0.5 mol) in dichloromethane (1000 mL) was added trifluoroacetic acid (100 mL)Stirring to the thin layer chromatography without raw materials,The system is poured into a saturated solution of sodium bicarbonate,Extracted with dichloromethane,Spin dry,Petroleum ether was beaten to give colorless needles 4 (75.6 g, 92.8%),
With trifluoroacetic acid; In water; for 1.0h; d). To the cyclopropylcyano acetal prepared above (7.28 g, 35.1 mmol) was added trifluoroacetic acid (100 mL) and water (4 mL). The solution was stirred for 1 h then poured into saturated NaHCO3 (1500 mL). The aqueous was extracted with ethyl acetate (3*300 mL). The combined organics were washed with brine, dried with MgSO4, and concentrated in vacuo to afford the ketone. This material was carried on to the next step without further purification. 1H NMR (500 Hz, CDCl3): delta 0.62-0.69 (m, 4H), 0.88-0.94 (m, 1H), 1.88-1.94 (m, 2H), 2.35-2.39 (m, 2H), 2.47-2.51 (m, 2H), 2.68-2.74 (m, 2H).
  • 2
  • [ 960370-97-2 ]
  • [ 765-30-0 ]
  • C13H20N2 [ No CAS ]
  • C13H20N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
e). To the ketone prepared in step d (6.0 g, 37 mmol) in dichloroethane (110 mL) was added cyclopropylamine (3.1 mL, 44 mmol). The solution was cooled to 0 C. (ice bath), and NaBH(OAc)3 (12 g, 55 mmol) and AcOH (2.8 mL, 48 mmol) were added. After 5 minutes the ice bath was removed. The reaction was stirred at room temperature for 4 h. The contents were diluted with CH2Cl2 (100 mL) poured in water (100 mL). The aqueous layer was brought to pH 2 with 5 N HCl. Following removal of the organic layer, the aqueous layer was brought to pH 12 with 5 N NaOH and extracted with 10% MeOH in CH2Cl2 (3×35 mL). The combined organics were dried with Na2SO4 and concentrated in vacuo. Silica gel chromatography (gradient of 5 to 10% ethyl acetate in hexanes with 2.5% triethylamine additive) gave the cis amine followed by the trans amine. 1H NMR (500 Hz, CDCl3, trans isomer): delta 0.15-0.17 (m, 2H), 0.25-0.29 (m, 2H), 0.34-0.37 (m, 4H), 0.58-0.63 (m, 1H), 1.22-1.31 (m, 4H), 1.84-1.90 (m, 4H), 1.96-2.00 (m, 1H), 2.38-2.40 (m, 1H).
  • 3
  • [ 960370-97-2 ]
  • [ 765-30-0 ]
  • [ 960370-99-4 ]
  • C13H20N2 [ No CAS ]
  • 4
  • [ 4746-97-8 ]
  • [ 960370-97-2 ]
 

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