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Structure of 76535-75-6

Chemical Structure| 76535-75-6

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Product Details of [ 76535-75-6 ]

CAS No. :76535-75-6
Formula : C14H26N2O4
M.W : 286.37
SMILES Code : O=C(N1CCN(C(OC(C)(C)C)=O)CC1)OC(C)(C)C
MDL No. :MFCD01435774
InChI Key :YROXEBCFDJQGOH-UHFFFAOYSA-N
Pubchem ID :545824

Safety of [ 76535-75-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 76535-75-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 84.34
TPSA ?

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

59.08 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.59
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

1.77
Log Po/w (WLOGP)?

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

1.71
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.

1.44
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

0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.86

Water Solubility

Log S (ESOL):?

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

-2.33
Solubility 1.33 mg/ml ; 0.00463 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.

-2.63
Solubility 0.673 mg/ml ; 0.00235 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

-1.46
Solubility 10.0 mg/ml ; 0.035 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.

-6.79 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

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<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)

2.68

Application In Synthesis of [ 76535-75-6 ]

* 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 [ 76535-75-6 ]

[ 76535-75-6 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 110-85-0 ]
  • [ 24424-99-5 ]
  • [ 76535-75-6 ]
YieldReaction ConditionsOperation in experiment
95% With iron oxide In ethanol at 20℃; for 0.416667 h; Green chemistry General procedure: A round-bottom flask (10 mL), which contains EtOH(5 mL), was charged with a solution of diboc (1–2 mmol),nano-Fe3O4 (3 molpercent, 0.007 g) and the amine (1 mmol). The mixture was stirred at room temperature for the appropriate time (Table 3). After completion of the reaction, the catalyst was collected by a magnet and separated from the solution of product and the remaining starting materials.After drying and evaporation of the solvent, the resulting solid was recrystallized from n-hexane or ethyl acetate(5 mL) to give the pure product. The recovered catalyst was washed with EtOH, dried and reused for the next run. The catalyst was recovered and reused for six times without any significant changes in the yield and the reaction time.
93%
Stage #1: With C12H24KO6(1+)*Br3H(1-) In ethanol at 20℃; for 0.0166667 h;
Stage #2: at 20℃; for 0.0166667 h;
For the N-boc protection of amines, to solution of diboc (1 mmol) in ethanol (5 ml) was added {K*18-crown-6]Br3}n (0.001 mmol). The solution was stirred at room temperature for 1 min. The amine (1 mmol) was then added and solution as stirred at room temperature for an appropriate time (table 1). After completion of the reaction, the solvent was removed by water bath distillation. To the residue was added ethyl acetate (5 ml) and the mixture was filtered (the catalyst is insoluble in n-hexane and ethyl acetate). The solid was washed with ethyl acetate ()10 ml*2) amd combined filtrates were reduced to dryness to yield the pure products.
87% With copper In neat (no solvent) at 20℃; for 0.25 h; General procedure: To a mixture of amine (1.0 mmol) and (Boc)2O (1.2 mmol), copper nano particles (0.1 mmol) was added with vigorous stirring at room temperature or 70 oC for the appropriate time (Scheme 2 and Table 2) until disappearance of the precursor amine was observed in the TLC. After completion, the reaction mixture was diluted with dry ether (5 mL) and catalyst was separated by filtration and the residue was washed with ether. The combined filtrate was evaporated to dryness and dried under vacuum. The N-Boc product is essentially pure on TLC but for getting analytical data the sample was passed through silica-gel (100-200 mesh) column using 10-30percent ethyl acetate in hexane as eluent. The physical data (m.p., FTIR, NMR) of the known compounds were found to be identical with those reported in the literature.
References: [1] Tetrahedron Letters, 2009, vol. 50, # 46, p. 6244 - 6246.
[2] Synthetic Communications, 2012, vol. 42, # 1, p. 25 - 32.
[3] Tetrahedron Letters, 2007, vol. 48, # 47, p. 8318 - 8322.
[4] Comptes Rendus Chimie, 2013, vol. 16, # 11, p. 962 - 966.
[5] Chinese Journal of Catalysis, 2013, vol. 34, # 9, p. 1730 - 1733.
[6] Tetrahedron Letters, 2017, vol. 58, # 7, p. 629 - 633.
[7] Journal of the Chinese Chemical Society, 2011, vol. 58, # 4, p. 538 - 543.
[8] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 3, p. 735 - 738.
  • 2
  • [ 110-85-0 ]
  • [ 24424-99-5 ]
  • [ 76535-75-6 ]
  • [ 57260-71-6 ]
YieldReaction ConditionsOperation in experiment
60% at 0℃; for 1 h; To a cold methylene chloride solution (10 ml) of piperazine (30.23 mmol, 2.60 g) was added methylene chloride solution (10 ml) of BOC anhydride (1.50 mmol) and the mixture was stirred at 0°C for 1 hour. After the reaction is complete, water is added and the aqueous K2CO3 solution is added to make the reaction mixture basic. All of the reaction mixture was extracted with methylene chloride and the product was isolated by column chromatography.
References: [1] Green Chemistry, 2014, vol. 16, # 7, p. 3635 - 3642.
[2] Journal of Heterocyclic Chemistry, 1990, vol. 27, # 6, p. 1559 - 1563.
[3] Russian Journal of Organic Chemistry, 2009, vol. 45, # 5, p. 788 - 791.
[4] Patent: KR2015/111825, 2015, A, . Location in patent: Paragraph 0722-0734.
[5] Journal of Medicinal Chemistry, 1992, vol. 35, # 21, p. 3845 - 3857.
[6] Journal of Medicinal Chemistry, 1992, vol. 35, # 21, p. 3845 - 3857.
[7] Tetrahedron Letters, 2006, vol. 47, # 46, p. 8039 - 8042.
[8] Patent: KR2016/108281, 2016, A, . Location in patent: Paragraph 0721-0724.
  • 3
  • [ 24424-99-5 ]
  • [ 57260-71-6 ]
  • [ 76535-75-6 ]
References: [1] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8283 - 8286.
  • 4
  • [ 24424-99-5 ]
  • [ 135841-26-8 ]
  • [ 76535-75-6 ]
  • [ 128019-59-0 ]
References: [1] Enantiomer, 2001, vol. 6, # 6, p. 343 - 345.
  • 5
  • [ 24424-99-5 ]
  • [ 76535-75-6 ]
References: [1] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8283 - 8286.
 

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