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Chemical Structure| 59702-31-7 Chemical Structure| 59702-31-7

Structure of 1-Ethylpiperazine-2,3-dione
CAS No.: 59702-31-7

Chemical Structure| 59702-31-7

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Product Details of [ 59702-31-7 ]

CAS No. :59702-31-7
Formula : C6H10N2O2
M.W : 142.16
SMILES Code : O=C1N(CC)CCNC1=O
MDL No. :MFCD00051825
InChI Key :ZBEKOEYCWKIMGU-UHFFFAOYSA-N
Pubchem ID :108812

Safety of [ 59702-31-7 ]

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

Computational Chemistry of [ 59702-31-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 42.77
TPSA ?

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

49.41 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.99
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

-0.43
Log Po/w (WLOGP)?

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

-1.8
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.

-0.96
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

0.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.4

Water Solubility

Log S (ESOL):?

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

-0.38
Solubility 58.7 mg/ml ; 0.413 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.

-0.14
Solubility 102.0 mg/ml ; 0.72 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

-0.92
Solubility 17.0 mg/ml ; 0.12 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

Low
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.

-7.47 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

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<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)

1.32

Application In Synthesis of [ 59702-31-7 ]

* 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 [ 59702-31-7 ]

[ 59702-31-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 85208-10-2 ]
  • [ 59703-00-3 ]
  • 6-<(+/-)-α-(2-aminothiazol-4-yl)-α-(4-ethyl-2,3-dioxopiperazin-1-ylcarbonylamino)acetamido>penicillanic acid [ No CAS ]
  • [ 59702-31-7 ]
  • 2
  • [ 75-44-5 ]
  • [ 59702-31-7 ]
  • [ 59703-00-3 ]
YieldReaction ConditionsOperation in experiment
With chloro-trimethyl-silane; triethylamine; In tetrahydrofuran; 1,4-dioxane; (2)--To a suspension of 0.71 g of the abovementioned 1-ethyl-2,3-dioxo-piperazine in 15 ml of anhydrous dioxane were added with stirring 0.70 g of trimethylsilyl chloride and 0.83 ml of triethylamine. The resulting mixture was stirred at room temperature for 20 hours to deposit triethylamine hydrochloride. This hydrochloride was separated by filtration, and the filtrate was dropped at 5 to 10 C. into a solution of 0.70 g of phosgene in 10 ml of anhydrous tetrahydrofuran. Subsequently, the resulting mixture was reacted at 5 to 10 C. for 30 minutes and at room temperature for 2 hours, and then the solvent was removed by distillation under reduced pressure to obtain 1.0 g of pale yellow crystals of 4-ethyl-2,3-dioxo-1-piperazinocarbonyl chloride. IR (KBr) cm-1: -- νC=O 1780, 1660
  • 3
  • [ 32315-10-9 ]
  • [ 59702-31-7 ]
  • [ 59703-00-3 ]
YieldReaction ConditionsOperation in experiment
94.3% With pyridine; dmap; chloro-trimethyl-silane; In dichloromethane; at -25 - -20℃; 1) taking N-ethyldioxypiperazine 14.2 g (0.10 mol),Transfer to a 500 mL three-necked flask, stir, and add 200 mL of dichloromethane.Cool down to -25 to -20 C, add 16.3 g (0.15 mol) TMCS,Control temperature -25 ~ -20 C, add 11.9g (0.15mol) pyridine,Adding 0.018 g of DMAP, adding 11.9 g (0.04 mol) of triphosgene in batches at a temperature of -25 to -20 C, and maintaining the reaction for 30-60 minutes;After the reaction was completed, suction filtration, washing with 30 mL of dichloromethane and distillation to dryness under reduced pressure.Add 100 mL of n-hexane to crystallize and filter by suction.Drying gave 19.3 g of N-ethylbisoxypiperazine chloride in a yield of 94.3%.
93.9% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 10 - 20℃; for 1.06667h;Green chemistry; add 85.2g ofdichloromethane, 14.2g(0.10mol)N-ethyl-2,3-dioxypiper in the reaction flaskReduce the temperature of oxazine to 15C, add 10.1g(0.034mol) triphosgene; control the temperature to 10-20C,add15.5g(0.102mol)dropwiseDBU, it took 34 minutes to complete the dripping, and the reaction was kept for 30 minutes; after the reaction, the dichloride ofN-ethyl-2,3-dioxypiperazinyl chloridewas obtained by suction filtrationMethane feed liquid (external standard contains 19.2g(0.094mol)N-ethyl-2,3-dioxypiperazine acid chloride, yield 93.9%); add to the filter residueAdd 30% sodium hydroxide solution and water to adjustpH=9.6, vacuum distillation to recoverDBU, the fraction is dried after potassium hydroxide to recover DBU.
1-Ethylpiperazine-2,3-dione (455 mg, 3.20 mmol, 1.00 eq.) was dissolved in dry dichloromethane (8.9 mL) under argon atmosphere at room temperature. After cooling to 0 C, dry triethylamine (616 pL, 4.42 mmol, 1.38 eq.) and then TMSCI (447 pL, 3.53 mmol, 1.10 eq.) were added and the resulting mixture stirred for one hour at room temperature.The reaction was then cooled to -30 C, triphosgene (361 mg, 1.21 mmol, 0.38 eq.) was added in one batch and stirring was continued for another hour. Thorough drying in vacuo yielded intermediate 4 as moisture sensitive foam, which was directly redissovled in dry dichloromethane (8.9 mL) for further synthesis. Meanwhile, D-(-)-a-Phenylglycine (1, 500 mg, 3.20 mmol. 1.00 eq.) was dissolved in dry dichloromethane (8.9 mL) under argon atmosphere at room temperature. Thereto, dry triethylamine (693 pL, 6.72 mmol, 2.10 eq.) and then TMSCI (894 pL, 7.04 mmol, 2.20 eq.) were added at 0 C and the resulting mixture stirred for two hours at room temperature. Afterwards, the beforehand prepared solution of intermediate 4 was added at -40 C and the reaction was stirred for 30 min., warmed to 0 C and stirred for another hour. The reaction was quenched via the addition of dest. water (ca. 10 mL). After in vacuo removal of dichloromethane, the resulting aqueous suspension was mixed with ethyl acetate (ca. 50 mL). The pH of the aqueous phase was adjusted to 8.0 via the addition of solid NaHCOs and the layers were then separated. The aqueous layer was washed with ethyl acetate (20 mL, 3 times). The aqueous phase was then adjusted to pH = 2.0 via the addition of aqueous concentrated HCI, before it was extracted with ethyl acetate (50 mL, 5 times). The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. Thus, Acid 5 (1.04 g, 3.04 mmol, 95%) was obtained as colorless foam with a residual content of ethyl acetate (ca. 5 wt-%).
 

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