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Chemical Structure| 2346-26-1 Chemical Structure| 2346-26-1

Structure of 2346-26-1

Chemical Structure| 2346-26-1

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Product Details of [ 2346-26-1 ]

CAS No. :2346-26-1
Formula : C3H3NO3
M.W : 101.06
SMILES Code : O=C(N1)OCC1=O
MDL No. :MFCD02691902
InChI Key :COWNFYYYZFRNOY-UHFFFAOYSA-N
Pubchem ID :97389

Safety of [ 2346-26-1 ]

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

Computational Chemistry of [ 2346-26-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 23.01
TPSA ?

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

55.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.37
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

-0.47
Log Po/w (WLOGP)?

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

-1.13
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.

-1.79
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

0.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.53

Water Solubility

Log S (ESOL):?

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

-0.17
Solubility 68.3 mg/ml ; 0.675 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.

-0.23
Solubility 59.9 mg/ml ; 0.593 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

-0.2
Solubility 63.3 mg/ml ; 0.627 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.

-7.25 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

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)

1.54

Application In Synthesis of [ 2346-26-1 ]

* 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 [ 2346-26-1 ]

[ 2346-26-1 ] Synthesis Path-Downstream   1~35

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YieldReaction ConditionsOperation in experiment
55% With potassium tert-butylate; In methanol; at 75℃; for 18h;Inert atmosphere; [00227] A solution of glycolamide (2.10 g, 28 mmol), diethylcarbonate (4.06 mL, 34.0 mmol), and KOtBu (3.14 g, 28 mmol) in MeOH (30 mL) was heated to 75C for 18 h under N2 gas. The mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted in a mixture of brine (100 mL) and 1M HCl (100 mL), and the aq phase was extracted with EtOAc (3X50 mL). The combined organic phases were dried over MgS04, filtered, and concentrated under reduced pressure to provide oxazolidine-2,4-dione as a solid (1.56 g, 55%). 1H NMR (300 MHz, DMSO) delta 11.8 (s, 1H), 4.75 (s, 2H)._
With potassium tert-butylate; In methanol;Heating / reflux; To a solution of glycolamide (14 g, 186 mmol) and diethyl carbonate (27.1 mL, 224 mmol) in methanol (200 mL) was added potassium t-butoxide (20.8 g, 186 mmol). The reaction mixture was refluxed overnight, then cooled to room temperature. The solvent was removed in vacuo. The residue was dissolved in brine, acidified with 2N HCl, then extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give 8.0 g of oxazolidinedione as a white solid.
With sodium methylate; In methanol; for 1.5h;Reflux; Step A: Oxazolidine-2,4-dione; To a solution of NaOMe (1.05 mmoles) in MeOH (21 ml) there are added 2-hydroxyacetamide (1 mmole) and diethyl carbonate (1.15 mmoles), and the reaction mixture is then heated at reflux for 1.5 hours. The reaction mixture is evaporated to dryness and then taken up in water. The aqueous phase is extracted with diethyl ether. The aqueous phase is acidified (pH 2) and then evaporated to dryness. The residue is triturated in AcOEt and filtered. The product obtained is purified on silica gel (c-Hexane/AcOEt; 1/1) to yield the title product in the form of a white powder.
With potassium tert-butylate; In methanol; for 20h;Reflux; Step 1 Oxazolidine-2,4-dione 2-Hydroxyacetamide (2.0 g, 26.6 mmol) and potassium tert-butoxide (3.0 g, 26.6 mmol) were dissolved in dry methanol (50 mL), added with diethyl carbonate (3.8 g, 31.9 mmol) and stirred at reflux for 20 hours. The reaction solution was cooled, concentrated under reduced pressure, dissolved in water and acidified to pH=2 with 6M hydrochloric acid solution. The mixture was extracted with ethyl acetate (100 mL*3), and the organic layer was washed with saturated brine and water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give oxazolidine-2,4-dione (1.2 g, crude product). 1H NMR (400 MHz, DMSO) 4.75 (s, 2H), 3.91 (s, 1H).

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  • (5R,6S)-6-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-3-(2,4-dioxo-oxazolidin-3-ylmethyl)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester [ No CAS ]
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YieldReaction ConditionsOperation in experiment
96% With triethylamine; In dichloromethane; PREPARATION A 3-Triphenylmethyl-1,3-<strong>[2346-26-1]oxazolidine-2,4-dione</strong> To a solution of 1,3-<strong>[2346-26-1]oxazolidine-2,4-dione</strong> (60.7 g, 0.600 mol) and triethylamine (60.7 g, 0.600 mol) in methylene chloride (500 mL) was added triphenylmethyl chloride (167.3 g, 0.600 mol). After 30 minutes, the thick white solid was collected by vacuum filtration, washed with water (2 L) and dried in a vacuum desicator to give the title compound (201.4 g, 96%). A portion was recrystallized from chloroform to give white plates: mp 216-218 C.
With triethylamine; In chloroform; ethyl acetate; C. 3-Triphenylmethyl-<strong>[2346-26-1]2,4-oxazolidinedione</strong> To a solution of 600 mg of <strong>[2346-26-1]2,4-oxazolidinedione</strong> and 601 mg of triethylamine in 7.0 ml of chloroform was added 1.66 g of triphenyl chloromethane and the reaction mixture stirred at room temperature for 30 minutes. The resulting mixture was dissolved in 250 ml of ethyl acetate and washed with water (3*50 ml) and brine (2*20 ml) and dried over sodium sulfate. Removal of the solvent gave 1.8 g of the desired product.
With triethylamine; In chloroform; ethyl acetate; C. 3-Triphenylmethyl-<strong>[2346-26-1]2,4-oxazolidinedione</strong> To a solution of 600 mg of <strong>[2346-26-1]2,4-oxazolidinedione</strong> and 601 mg of triethylamine in 7.0 ml of chloroform was added 1.66 g of triphenyl chloromethane and the reaction mixture stirred at room temperature for 30 minutes. The resulting mixture was dissolved in 250 ml of ethyl acetate and washed with water (3 x 50 ml) and brine (2 x 20 ml) and dried over sodium sulfate. Removal of the solvent gave 1.8 g of the desired product.
With triethylamine; In dichloromethane; at 20℃; for 0.666667h; To a solution of the above obtained oxazolidinedione (4.6 g, 45 mmol) in CH2Cl2 (50 mL) were added TrCl (12.6 g, 45 mmol) and Et3N (6.3 mL, 45 mmol). The reaction mixture was stirred at room temperature for 40 min, then partitioned between water and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the N-trityl OZD product.

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Technical Information

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