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Chemical Structure| 626-35-7 Chemical Structure| 626-35-7

Structure of Ethyl nitroacetate
CAS No.: 626-35-7

Chemical Structure| 626-35-7

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Product Citations

Product Citations

Thoenen, Michael ; Scherschel, Nicholas F ; Piercey, Davin G ;

Abstract: Diethyl furoxan dicarboxylate (DFD) is a starting material for fields as diverse as drug discovery, energetics, and any application where a furoxan or furazan may be desired. As with many disubstituted furoxans, they are synthesized via the dimerization of the appropriate nitrile oxide. Past procedures to form DFD involve low-yield destructive nitrations, multiple steps, halogenated solvents, or heavy or precious metals. Although these methods are functional enough for lab-scale preparations of DFD, they do not hold up well for economical scale-up. Our reported procedure improves the synthesis of DFD such that it is available from economical and commercially available starting materials in a single-step, one-pot, high-yield (98.5%) synthesis of material with a trivial workup in high purity (98.2% by 1H quantitative NMR against a 2,4,6-trimethoxy-1,3,5-triazene standard). This improved procedure requires no organic solvents or heavy metals and is the most scalable preparation for this material to date.

Keywords: nitrile oxide ; diethyl furoxan-3,4-dicarboxylate ; esters ; energetic materials

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Alternative Products

Product Details of [ 626-35-7 ]

CAS No. :626-35-7
Formula : C4H7NO4
M.W : 133.10
SMILES Code : O=C(OCC)C[N+]([O-])=O
MDL No. :MFCD00007403
InChI Key :FTKASJMIPSSXBP-UHFFFAOYSA-N
Pubchem ID :69379

Safety of [ 626-35-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H227
Precautionary Statements:P501-P210-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313-P403+P235

Computational Chemistry of [ 626-35-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 30.73
TPSA ?

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

72.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.94
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

0.48
Log Po/w (WLOGP)?

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

-0.17
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.

-0.9
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

-1.55
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.24

Water Solubility

Log S (ESOL):?

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

-0.7
Solubility 26.3 mg/ml ; 0.198 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.

-1.56
Solubility 3.63 mg/ml ; 0.0273 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

-0.11
Solubility 102.0 mg/ml ; 0.769 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

No
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.

-6.77 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

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<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)

2.13

Application In Synthesis of [ 626-35-7 ]

* 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 [ 626-35-7 ]

[ 626-35-7 ] Synthesis Path-Downstream   1~8

  • 2
  • [ 626-35-7 ]
  • [ 54439-75-7 ]
  • (4α,5β)-ethyl 4,6-dichloro-8-oxo-1-oxa-2-azaspiro<4,5>deca-2,6,9-triene-3-carboxylate [ No CAS ]
  • 3
  • [ 626-35-7 ]
  • [ 54439-75-7 ]
  • ethyl (E)-3-(2'-chloro-4'-methoxyphenyl)-2-nitroacrylate [ No CAS ]
  • ethyl (Z)-3-(2'-chloro-4'-methoxyphenyl)-2-nitroacrylate [ No CAS ]
  • 4
  • [ 626-35-7 ]
  • [ 43192-31-0 ]
  • [ 57543-36-9 ]
  • (4α,5β)-ethyl 4,6-dibromo-8-oxo-1-oxa-2-azaspiro<4,5>deca-2,6,9-triene-3-carboxylate [ No CAS ]
  • (4α,5β)-ethyl 4,6,9-tribromo-8-oxo-1-oxa-2-azaspiro<4,5>deca-2,6,9-triene-3-carboxylate [ No CAS ]
  • 5
  • [ 530-48-3 ]
  • [ 626-35-7 ]
  • [ 163520-33-0 ]
  • 6
  • [ 626-35-7 ]
  • [ 287172-82-1 ]
  • [ 122-51-0 ]
  • [ 1422386-57-9 ]
YieldReaction ConditionsOperation in experiment
15% With acetic acid; In ethanol; at 70℃; for 92.0h;Sealed tube; [00395] Intermediate 35A. Ethyl 3-((3-chloro-2,6-difluorophenyl)amino)-2- nitroacrylate: A sealed, high pressure vial containing a clear, colorless solution of ethyl nitroacetate (0.170 ml, 1.529 mmol), triethylorthoformate (0.255 ml, 1.529 mmol), 3- chloro-2,6-difluoroaniline (0.250 g, 1.529 mmol), acetic acid (0.026 ml, 0.459 mmol), and EtOH (1.529 ml) was heated to 70 C. After 92 h, the clear, dark yellow solution was concentrated to give an orange oil. Purification by normal phase chromatography gave Intermediate 35A (0.0721 g, 15%) as a yellow solid. MS(ESI) m/z: 307.0 (M+H)+.
  • 7
  • [ 626-35-7 ]
  • [ 31599-60-7 ]
  • [ 5724-56-1 ]
  • 8
  • [ 626-35-7 ]
  • [ 32566-01-1 ]
  • [ 110059-97-7 ]
 

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