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Chemical Structure| 4975-73-9

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Product Details of [ 4975-73-9 ]

CAS No. :4975-73-9
Formula : C17H31N3O
M.W : 293.45
SMILES Code : N1(/C(NC2CCCCC2)=N\C3CCCCC3)CCOCC1
MDL No. :MFCD00063252
InChI Key :OZNYZQOTXQSUJM-UHFFFAOYSA-N
Pubchem ID :21079

Safety of [ 4975-73-9 ]

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

Computational Chemistry of [ 4975-73-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 0
Fraction Csp3 0.94
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 91.87
TPSA ?

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

36.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.42
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

2.88
Log Po/w (WLOGP)?

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

2.55
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.

2.72
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

2.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.9

Water Solubility

Log S (ESOL):?

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

-3.21
Solubility 0.181 mg/ml ; 0.000617 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.31
Solubility 0.142 mg/ml ; 0.000485 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

-3.08
Solubility 0.246 mg/ml ; 0.000839 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

Yes
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.

-6.05 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

0.0
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

2.0 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<0.0
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)

3.51

Application In Synthesis of [ 4975-73-9 ]

* 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 [ 4975-73-9 ]

[ 4975-73-9 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 110-91-8 ]
  • [ 538-75-0 ]
  • [ 4975-73-9 ]
YieldReaction ConditionsOperation in experiment
98% at 50℃; for 2 h; Inert atmosphere General procedure: A 10 mL Schlenk tube was charged with III (0.0128 g, 0.0075 mmol), N,N'-diisopropylcarbodiimide (0.189 g, 1.5 mmol), and aniline (0.140 g, 1.5 mmol) under dried argon. The resulting mixture was stirred at 25 °C for 30 min. The reaction mixture was extracted with ether and filtered to give a clean solution. After removing the solvent under vacuum, the residue was recrystallized in ether to provide a white solid 1 in >99percent yield.
96% With zinc(II) oxide In toluene at 110℃; for 10 h; General procedure: A mixture of amine (1 mmol), carbodiimide (1.1 mmol) and nanocrystalline ZnO (20 mol percent, 0.016 g) was stirred in toluene (1 mL) at 80 °C for 8 h (for aromatic and aliphatic primary amines) or at 110 °C for 10 h (for secondary amines). The progress of the reaction was monitored by TLC analysis. At the end of the reaction, the reaction mixture was allowed to cool to room temperature, centrifuged and filtered the supernatant through a sintered funnel. The catalyst was then washed with ethyl acetate, centrifuged and filtered. The combined filtrate was concentrated under reduced pressure, and further purified by column chromatography on neutral alumina using ethyl acetate/hexane as the eluent to afford the desired product in good yields.
96% With iron(II) acetate In toluene at 140℃; for 5 h; Inert atmosphere General procedure: A Schlenk tube under nitrogen was charged with Fe(OAc)2 (8.70 mg, 0.05 mmol), the corresponding amine (1 mmol) and carbodiimide (1.2 mmol) and toluene (2 mL). The resulting suspension was heated at 140 oC and the progress of the reaction was monitored by TLC. At the end of the reaction, the reaction mixture was allowed to cool to room temperature and then hydrolyzed with water (5 mL), extracted with dichloromethane (3 10 mL), dried over anhydrous Na2SO4 and filtered. Then, the solvent was evaporated under reduced pressure to give the crude product which was purified by recrystallization method in hexane or diethyl ether and also by column chromatography to afford the desired products in good yields.
96% With 1,3-di-tert-butylimidazol-2-ylidene:Mg[N(SiMe3)2]2 In toluene at 110℃; for 24 h; Schlenk technique; Inert atmosphere; Glovebox General procedure: A 30 mL Schlenk tube under inert atmosphere (N2-glovebox) was charged with the catalyst ItBu:Mg[N(SiMe3)2]2 (0.03 equiv), secondary amine (1.0 equiv), and toluene (5 mL). To this mixture carbodiimides (1.0 equiv) was added. The flask was then closed to prevent evaporation of amines with low boiling points, and the resulting mixture was heated to 110 °C for the desired time. The solvent was removed under reduced pressure; the residue was extracted with hexane (3 x 15 mL) and filtered to give a clean solution. After removing the hexane under reduced pressure, the final products were obtained.

References: [1] Journal of Organic Chemistry, 2008, vol. 73, # 22, p. 8966 - 8972.
[2] Tetrahedron, 2011, vol. 67, # 45, p. 8790 - 8799.
[3] Tetrahedron, 2012, vol. 68, # 29, p. 5730 - 5737.
[4] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5156 - 5158.
[5] Journal of Organometallic Chemistry, 2014, vol. 769, p. 112 - 118.
[6] Journal of Organic Chemistry, 2009, vol. 74, # 16, p. 6347 - 6349.
[7] Journal of Organometallic Chemistry, 2012, vol. 713, p. 27 - 34.
[8] Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 8, p. 1211 - 1220.
  • 2
  • [ 108-91-8 ]
  • [ 4975-73-9 ]
References: [1] Journal of Medicinal Chemistry, 1994, vol. 37, # 22, p. 3693 - 3700.
  • 3
  • [ 36903-85-2 ]
  • [ 4975-73-9 ]
References: [1] Journal of Medicinal Chemistry, 1994, vol. 37, # 22, p. 3693 - 3700.
 

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