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Chemical Structure| 117565-57-8

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Product Details of [ 117565-57-8 ]

CAS No. :117565-57-8
Formula : C12H21NO3
M.W : 227.30
SMILES Code : O=C(N1CC(CC)C(CC1)=O)OC(C)(C)C
MDL No. :MFCD08460961
InChI Key :HGJKZGGZDSJORL-UHFFFAOYSA-N
Pubchem ID :22278903

Safety of [ 117565-57-8 ]

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

Computational Chemistry of [ 117565-57-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 66.41
TPSA ?

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

46.61 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.81
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

1.49
Log Po/w (WLOGP)?

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

1.84
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.

1.33
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

1.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.82

Water Solubility

Log S (ESOL):?

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

-1.92
Solubility 2.71 mg/ml ; 0.0119 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.

-2.08
Solubility 1.91 mg/ml ; 0.00839 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

-1.96
Solubility 2.48 mg/ml ; 0.0109 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.

-6.63 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)

2.68

Application In Synthesis of [ 117565-57-8 ]

* 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 [ 117565-57-8 ]

[ 117565-57-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 104777-74-4 ]
  • [ 24424-99-5 ]
  • [ 117565-57-8 ]
YieldReaction ConditionsOperation in experiment
83% Compound 26 (2.90 g, 10.2 mmol) was suspended in 6 N HCl (85 ml) and refluxed for 16 h. The product was concentrated and azeotroped three times with isopropanol to give a yellow solid. The solid was dissolved in 1:1 CH2Cl2:MeOH (50 ml) and Et3N (3.08 g, 4.3 ml, 30.5 mmol) and di-t-butyl dicarbonate (3.32 g, 15.2 mmol) were added. The mixture was stirred at 23 C. for 16 h, then concentrated. 0.5 N NaOH (50 ml) was added and the mixture extracted with CH2Cl2. The combined organic extracts were dried (MgSO4), filtered, and concentrated. Purification by silica gel chromatography (eluant: 10% EtOAc-hexane) gave 1.92 g (8.46 mmol, 83%) of the product 27A as a colorless oil. MS (ES for M+1): m/e 228
  • 2
  • [ 120-72-9 ]
  • [ 117565-57-8 ]
  • [ 604010-25-5 ]
YieldReaction ConditionsOperation in experiment
PREPARATION 184; 1-(1-tert-Butoxycarbonyl-3-ethyl-piperidin-4-yl)-1H-indole; Dissolve 1H-Indole (10 g, 50.2 mmol) and 2, 6-Dimethyl-4-oxo-piperidine-1- carboxylic acid tert-butyl ester (8.62 g, 55.2 mmol) in glacial acetic acid (100 mL), add sodium triacetoxyborohydride (15.96 g, 75.3 mmol) and heat the mixture to 70C for 20 h. Cool the reaction mixture in an ice bath and made basic with 5N sodium hydroxide solution. Extract the mixture with methylene chloride, wash with water, brine and dry over sodium sulphate to yield the title compound. Flash chromatography using a gradient of ethyl acetate in hexanes yields the pure product. ESMS n ? lz (relative intensity) ES (M+H) : 329.1.
  • 3
  • [ 79099-07-3 ]
  • [ 75-03-6 ]
  • [ 117565-57-8 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In ethyl acetate; acetonitrile; benzene; Step 1 A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5 g, 25.1 mmol), pyrollidine (5 mL) and p-toluenesulfonic acid (25 mg) in benzene (100 mL) was heated at reflux for 16 h with azeotropic distillation of water. The resulting enamine solution was cooled to rt and concentrated. The crude enamine was dissolved in acetonitrile (50 mL); iodoethane (4.67 g, 30.1 mmol.) was added and the mixture was heated at 100 C. for 0.5 h, cooled to rt and concentrated. The mixture was dissolved in ethyl acetate (200 mL), washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The extract was dried over magnesium sulfate, filtered and concentrated. The crude compound was purified by silica gel chromatography (80% hexanes/20% ethyl acetate) to afford 3-ethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (680 mg). 1H-NMR (CDCl3, 300 MHz) delta: 0.95 (t, 3H), 1.26-1.42 (m, 1H), 1.50 (s, 9H), 1.69-1.85 (m, 1H), 2.30 (br s, 1H), 2.43 (q, 2H), 2.90-4.36 (m, 4H).
680 mg With toluene-4-sulfonic acid; In benzene; for 16h;Reflux; Step 1 A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5 g, 25.1 mmol), pyrolidine (5 mL) and p-toluenesulfonic acid (25 mg) in benzene (100 mL) was heated at reflux for 16 h with azeotropic distillation of water. The resulting enamine solution was cooled to rt and concentrated. The crude enamine was dissolved in acetonitrile (50 mL); iodoethane (4.67 g, 30.1 mmoL) was added and the mixture was heated at 100 C. for 0.5 h, cooled to rt and concentrated. The mixture was dissolved in ethyl acetate (200 mL), washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The extract was dried over magnesium sulfate, filtered and concentrated. The crude compound was purified by silica gel chromatography (80% hexanes/20% ethyl acetate) to afford 3-ethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (680 mg). 1H-NMR (CDCl3, 300 MHz) delta: 0.95 (t, 3H), 1.26-1.42 (m, 1H), 1.50 (s, 9H), 1.69-1.85 (m, 1H), 2.30 (br s, 1H), 2.43 (q, 2H), 2.90-4.36 (m, 4H).
  • 4
  • [ 37595-74-7 ]
  • [ 117565-57-8 ]
  • [ 1268816-83-6 ]
YieldReaction ConditionsOperation in experiment
42% [Example 73] tert-Butyl 3-ethyl-4-[2-(5-methanesulfonylindol-1-ylmethyl)pyridin-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (1) tert-Butyl 3-ethyl-4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyridine-1-carboxylate Under N2 atmosphere, a solution of 1.0M lithium bis(trimethylsilyl)amide-tetrahydrofuran solution (4.3 mL, 4.3 mmol) in dry tetrahydrofuran (20 mL) was cooled to -78C. To this was added dropwise a solution of <strong>[117565-57-8]tert-butyl 3-ethyl-4-oxopiperidine-1-carboxylate</strong> (881 mg, 3.88 mmol) in dry tetrahydrofuran (5 mL). After stirring at - 78C for 30 minutes, the reaction mixture was added dropwise a solution of N-phenylbis(trifluorometanesulfonimide) (1.4 g, 3.88 mmol) in dry tetrahydrofuran (5 mL). The reaction mixture was slowly warmed up to 0C. After stirring for 1 hour, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/chloroform = 8/1 ? 0/100), to give the title compound as a colorless oil (581 mg, yield 42%). 1H NMR (CDCl3 400 MHz): delta= 1.01 (3H, t, J = 7 Hz), 1.48 (9H, s), 1.3-1.6 (1H, m), 1.6-1.8 (1H, m), 2.2-2.5 (1H, m), 3.2-3.5 (1H, m), 3.7-4.0 (2H, m), 4.0-4.5 (1H, m), 5.74 (1H, br s).
  • 5
  • [ 117565-57-8 ]
  • [ 1268816-84-7 ]
  • 6
  • [ 117565-57-8 ]
  • 4-amino-3-ethylpiperidin-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium 10% on activated carbon; ammonium formate; In methanol; at 60℃; for 2h; A solution of /e/7-butyl 3-ethyl-4-oxopiperidine-l-carboxylate (1.00 g, 4.40 mmol) and ammonium formate (1.11 g, 17.6 mmol) in methanol (30 mL) was stirred for 10 minutes at room temperature. Palladium on carbon (10 wt %, 0.140 g, 0.132 mmol) was added and the reaction mixture was stirred at 60C for 2 hours. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give the title compound as a light brown syrup (0.962 g, 96%) which was used without further purification.
  • 7
  • [ 593-66-8 ]
  • [ 79099-07-3 ]
  • [ 117565-57-8 ]
YieldReaction ConditionsOperation in experiment
Under nitrogen protection at -70 C, LDA (2 M, 158.09 mL, 2.52 eq.) was added dropwise to a solution of 4-oxoperidine-1-formic acid tert-butyl ester (25.00 g, 125.47 mmol, 1.00 eq.) in THF (200.00 mL). Thirty minutes later, ethylene iodide (78.27 g, 501.88 mmol, 40.14 mL, 4.00 eq.) was added to the above solution at - 70 C, and then the mixture was stirred at room temperature (30 C) for 16 hours. TLC showed that there were still raw materials left. The reaction solution was quenched with saturated ammonium chloride solution (100 mL) and partitioned between ethyl acetate (100 mL) and water (200 mL). The aqueous solution was extracted with ethyl acetate (100 mL × 1). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate (50 g), and concentrated to a light yellow oily substance. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to give compound 21A. LCMS (ESI) (5-95AB): m/z: 128.1 [M+1-100].
 

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Technical Information

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