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Structure of 393781-71-0

Chemical Structure| 393781-71-0

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Product Details of [ 393781-71-0 ]

CAS No. :393781-71-0
Formula : C11H22N2O2
M.W : 214.31
SMILES Code : C(=O)(OC(C)(C)C)N1CCNCC1CC
MDL No. :MFCD03265490
InChI Key :CTCGRXDGXGUOTE-UHFFFAOYSA-N
Pubchem ID :18004789

Safety of [ 393781-71-0 ]

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

Computational Chemistry of [ 393781-71-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.91
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 68.12
TPSA ?

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

41.57 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.82
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

1.42
Log Po/w (WLOGP)?

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

0.84
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.

1.15
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

0.97
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.44

Water Solubility

Log S (ESOL):?

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

-1.8
Solubility 3.4 mg/ml ; 0.0159 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.

-1.9
Solubility 2.71 mg/ml ; 0.0127 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

-1.84
Solubility 3.06 mg/ml ; 0.0143 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.

-6.6 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

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)

2.75

Application In Synthesis of [ 393781-71-0 ]

* 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 [ 393781-71-0 ]

[ 393781-71-0 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 393781-71-0 ]
  • [ 49584-26-1 ]
  • [ 1244740-40-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; To a solution of 1 ,1-dimethylethyl 2-ethyl-1-piperazinecarboxylate (100mg, 0.467 mmol) in DCM (5ml_) was added di-isopropylethylamine (0.253mL, 1.447 mmol), followed by gradual addition of 4-cyanobenzenesulfonyl chloride (103mg, 0.513 mmol). The reaction mixture was allowed to stir for 1 hour. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then with distilled water (1OmL). The organic layer was dried (MgSO4), filtered and reduced in vacuo to yield 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate as a crude transparent oil (173mg), MS ES+ve m/z 280 (M+H-100). To 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate (173mg, 0.456 mmol) was added hydrogen chloride 1 M solution in 1 ,4 dioxane (1OmL) solution, followed by the addition of 3 drops of water. The reaction mixture was allowed to stir for 14hours. After this time, 5M aqueous HCI (1 ml) was added and the mixture was stirred for 12hours. The reaction mixture was concentrated in vacuo to yield colourless oil. The colourless oil was dissolved in methanol (1 OmL) and passed down a SCX-2 column washing with two column volumes of methanol and eluting the product with 2N ammonia solution in methanol (three column volumes). The fraction containing eluted product was reduced in vacuo to yield 4-[(3-ethyl-1- piperazinyl)sulfonyl]benzonitrile (99mg) as a transparent oil, MS ES+ve m/z 280 (M+H).To a solution of 4-[(3-ethyl-1-piperazinyl)sulfonyl]benzonitrile (99mg, 0.354mol) in tetrahydrofuran (1OmL) was added triethylamine (0.074mL, 0.532mmol) followed by drop wise addition of benzoyl chloride (0.045mL, 0.390mmol). The reaction mixture was allowed to stir for 30minut.es. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then 0.1 M hydrochloric acid (1OmL). The organic layer was dried with (MgSO4), filtered and concentrated in vacuo to yield 144mg colourless oil. The oil was dissolved in minimum volume of hot ethyl acetate (~2ml), hot iso-hexane (10ml) was then added and allowed to cool to room temperature. The supernatant was decanted off, and residual solid triturated with diethyl ether (50ml), to yield a white solid (67mg, 37%).1H-NMR (CDCI3) delta 0.65-1.19 (3H, br m), 1.78-1.98 (2H, m), 2.20-2.40 (1 H, m), 2.40- 2.57 (1 H, m), 2.96-3.48 (1 H, m), 3.48-3.96 (3H, m), 4.21-5.01 (1 H, m), 7.28-7.31 (2H, m), 7.36-7.45 (3H, m), 7.81-7.89 (4H, m).MS ES+ve m/z 384 (M+H).The single enantiomers were isolated from the racemic 4-[3-ethyl-4-(phenylcarbonyl)-1-piperazinyl]sulfonyl}benzonitrile (53mg) via chiral preparative chromatography using the following conditions:- Column: Chiralpak IC (20mm x 250mm, 5mum)- Eluent: Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =17. Omls/min- U.V. Absorbance (S) 215nm- Autosampler injection (250mul of sample in 20%Heptane/30%EtOH/50%DMF on column)- lsocratic Run time = 30 minutesIsolated enantiomers were analysed via chiral analytical chromatography using the following conditions:- Chiralpak IC (4.6mm x 250mm, 5mum)- Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =1. Omls/min- U.V. Absorbance (at) 215nm- Autosampler injection (1 Omul of sample in mobile phase on column)- lsocratic Run time = 30 minutesIsolated compounds: Example 5a: Faster running enantiomer (4-[(3S)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile or 4-[(3R)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile, 16mg)Retention time 19.37min
  • 2
  • [ 393781-71-0 ]
  • 6-[5-(difluoromethyl)pyridin-2-yl]oxy}quinoline-2-carboxylic acid [ No CAS ]
  • tert-butyl (2R)-4-[(6-[5-(difluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]-2-ethylpiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% Example 55A tert-butyl (2R)-4-[(6-[5-(difluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]-2-ethylpiperazine-1-carboxylate The product from Example 14A (300 mg, 0.95 mmol) was subjected to the conditions described in Example 14B, substituting <strong>[393781-71-0](R)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> for tert-butyl piperazine-1-carboxylate to give the titled compound (470 mg, 97%).
  • 3
  • [ 393781-71-0 ]
  • 6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinoline-2-carboxylic acid [ No CAS ]
  • [(3R)-3-ethylpiperazin-1-yl](6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)methanone [ No CAS ]
  • 4
  • [ 393781-71-0 ]
  • 6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinoline-2-carboxylic acid [ No CAS ]
  • tert-butyl (2R)-2-ethyl-4-[(6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
67.5% Example 16A tert-butyl (2R)-2-ethyl-4-[(6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]piperazine-1-carboxylate. The product from Example 1D (200 mg, 0.59 mmol) was subjected to the conditions described in Example 11, substituting <strong>[393781-71-0](R)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> for 4-(piperidin-4-yl)morpholine to give the titled compound (238 mg, 67.5%).
  • 5
  • [ 393781-71-0 ]
  • [ 55676-22-7 ]
  • (±)-tert-butyl 4-(5-acetyl-2-pyridyl)-2-ethylpiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85.0℃; for 12.0h; To a solution of 1-(6-chloro-3-pyridyl)ethanone (4.00 g, 24.9 mmol; CAS36357-38-7) in ACN (8 mL) was added DIPEA (9.67 g, 74.8 mmol) and <strong>[393781-71-0](±)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> (6.41 g, 29.9 mmol; CAS393781-71-0). The reaction mixture was stirred at 85 C. for 12 hours. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (petroleum ether:ethyl acetate=30:1 to 5:1) to give the title compound (8.30 g, 100% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 8.75 (d, J=2.0 Hz, 1H), 8.03 (dd, J=2.4, 9.2 Hz, 1H), 6.58 (d, J=8.8 Hz, 1H), 4.34 (d, J=13.2 Hz, 1H), 4.27 (d, J=10.4 Hz, 1H), 4.13 (q, J=7.2 Hz, 1H), 4.02 (s, 1H), 3.27 (dd, J=4.0, 13.2 Hz, 1H), 3.20-3.04 (m, 2H), 2.51 (s, 3H), 1.63-1.50 (m, 2H), 1.49 (s, 9H), 0.90 (t, J=7.2 Hz, 3H).
  • 6
  • [ 393781-71-0 ]
  • C21H32N4O3 [ No CAS ]
  • 7
  • [ 393781-71-0 ]
  • (±)-tert-butyl 2-ethyl-4-[5-(2-sulfanylpyrimidin-4-yl)-2-pyridyl]piperazine-1-carboxylate [ No CAS ]
  • 8
  • [ 393781-71-0 ]
  • (±)-tert-butyl 2-ethyl-4-[5-(2-methylsulfanylpyrimidin-4-yl)-2-pyridyl]piperazine-1-carboxylate [ No CAS ]
  • 9
  • [ 393781-71-0 ]
  • (+)-tert-butyl 2-ethyl-4-[5-(2-methylsulfonylpyrimidin-4-yl)-2-pyridyl]piperazine-1-carboxylate [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 393781-71-0 ]

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