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Chemical Structure| 252882-61-4 Chemical Structure| 252882-61-4

Structure of 252882-61-4

Chemical Structure| 252882-61-4

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Product Details of [ 252882-61-4 ]

CAS No. :252882-61-4
Formula : C12H14N2O
M.W : 202.25
SMILES Code : N1CCC3(CC1)C2=CC=CC=C2NC3=O
MDL No. :MFCD12198581
InChI Key :SXOVJOBXZPCKRA-UHFFFAOYSA-N
Pubchem ID :18435788

Safety of [ 252882-61-4 ]

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

Computational Chemistry of [ 252882-61-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.42
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 65.45
TPSA ?

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

41.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.87
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

0.69
Log Po/w (WLOGP)?

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

0.31
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.

1.45
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

2.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

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

-1.82
Solubility 3.03 mg/ml ; 0.015 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.

-1.13
Solubility 15.0 mg/ml ; 0.074 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

-4.04
Solubility 0.0183 mg/ml ; 0.0000906 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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

Yes
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.

-7.04 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)

2.19

Application In Synthesis of [ 252882-61-4 ]

* 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.

  • Upstream synthesis route of [ 252882-61-4 ]
  • Downstream synthetic route of [ 252882-61-4 ]

[ 252882-61-4 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 1086063-19-5 ]
  • [ 252882-61-4 ]
YieldReaction ConditionsOperation in experiment
90.2% With hydrogen In methanol at 20℃; for 15 h; Process 1Production of spiro(indole-3,4'-piperidine)-2(1H)-oneSpiro(indole-3,4'-piperidine)-2(1H)-one was produced by the method described below.Under an argon atmosphere, a tetrahydrofuran solution (20 mL) of oxindole (3.00 g, 22.5 mmol) and a tetrahydrofuran solution (20 mL) of benzylbis(2-chloroethyl)amine (5.20 g, 22.5 mmol) were added sequentially to a tetrahydrofuran solution (100 mL) of sodium hydride (1.60 g, 67.6 mmol) at room temperature. The mixture was stirred at the same temperature for 1 hour and further stirred at 90° C. for 3 hours. The reaction solution was cooled to room temperature, and then added with a tetrahydrofuran solution (10 mL) of sodium hydride (0.540 g, 22.5 mmol) and stirred further at 90° C. for 12 hours. The reaction solution was added with saturated ammonium-chloride aqueous solution and stirred at room temperature for 10 minutes. The mixed solution was poured into the mixed solution of a saturated aqueous solution of sodium hydrogen carbonate and brine, then extracted with ethyl acetate. The organic layer was dried with anhydrous sodium sulfate, followed by a vacuum concentration. The resultant residue was purified by silica-gel chromatography (chloroform:methanol=20:1) and 1'-benzylspiro(indole-3,4'-piperidine)-2(1H)-one (2.94 g, 44.6percent) was obtained as a yellow amorphous solid.1H-NMR (400 MHz, CDCl3) δ; 1.78-1.93 (m, 2H), 1.95-2.06 (m, 2H), 2.65-2.77 (m, 2H), 2.87-3.00 (m, 2H), 3.69 (s, 2H), 6.90 (d, J=7.6 Hz, 1H), 7.02(t, J=7.6 Hz, 1H), 7.20 (t, J=7.6 Hz, 1H), 7.26 (t, J=6.2 Hz, 1H), 7.34 (t, J=7.6 Hz, 2H), 7.40-7.41(m, 3H), 8.72 (s, 1H).To a methanol solution (5 mL) of 1'-benzylspiro(indole-3,4'-piperidine)-2(1H)-one (300 mg, 1.03 mmol), 10percent palladium carbon (30.0 mg) was added. The mixture was stirred under a hydrogen atmosphere at room temperature for 15 hours. The reaction solution was filtered using celite followed by a vacuum concentration, and spiro(indole-3,4'-piperidine)-2(1H)-one (187 mg, 90.2percent) was obtained as a colorless amorphous solid.1H-NMR (400 MHz, CDCl3) δ; 1.73-1.78 (m, 2H), 1.88-1.94 (m, 2H), 3.06-3.12 (m, 2H), 3.35-3.41 (m, 2H), 6.92 (d, J=7.7 Hz, 1H), 7.04 (t, J=7.7 Hz, 1H), 7.22 (t, J=7.7 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 8.70 (br, 1H).
78% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 15 h; Step 2A solution of 1’-benzylspiro[indoline-3,4’-piperidin]-2-one 2a (5 g, 17.10 mmol, 1 eq.)in methanol (100 ml) was hydrogenated at RT with 10percent Pd/C (0.18 g) as a catalyst for15h. The catalyst was filtered off and the solvent was evaporated under vacuum. Theresidue was then recrystallized from DIPE/acetonitrile to give 2.7 g (78percent yield) of spiro [indoline-3 ,4’-piperidin] -2-one 2b.
References: [1] Patent: US2008/306102, 2008, A1, . Location in patent: Page/Page column 12.
[2] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 94 - 97.
[3] Patent: WO2014/60411, 2014, A1, . Location in patent: Page/Page column 36.
  • 2
  • [ 252882-60-3 ]
  • [ 252882-61-4 ]
References: [1] Patent: WO2007/28638, 2007, A1, . Location in patent: Page/Page column 96.
[2] Patent: US6172076, 2001, B2, .
[3] Patent: WO2008/144266, 2008, A1, . Location in patent: Page/Page column 29.
  • 3
  • [ 59-48-3 ]
  • [ 252882-61-4 ]
References: [1] Patent: US6172076, 2001, B2, .
[2] Patent: WO2008/144266, 2008, A1, .
[3] Patent: US2008/306102, 2008, A1, .
 

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