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Chemical Structure| 1010814-94-4 Chemical Structure| 1010814-94-4

Structure of 1010814-94-4

Chemical Structure| 1010814-94-4

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Product Details of [ 1010814-94-4 ]

CAS No. :1010814-94-4
Formula : C16H27NO5
M.W : 313.39
SMILES Code : O=C(N1CC(CC(OC(C)(C)C)=O)C(CC1)=O)OC(C)(C)C
MDL No. :MFCD11111810
InChI Key :ALIVCUSTZCGWKQ-UHFFFAOYSA-N
Pubchem ID :49759529

Safety of [ 1010814-94-4 ]

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

Computational Chemistry of [ 1010814-94-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 0
Fraction Csp3 0.81
Num. rotatable bonds 7
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 86.96
TPSA ?

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

72.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.49
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

1.41
Log Po/w (WLOGP)?

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

2.16
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.

1.44
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

2.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.11

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 1.94 mg/ml ; 0.00618 mol/l
Class?

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

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.55
Solubility 0.893 mg/ml ; 0.00285 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

-2.45
Solubility 1.11 mg/ml ; 0.00355 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.

-7.21 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

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<0.0
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)

3.41

Application In Synthesis of [ 1010814-94-4 ]

* 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.

  • Downstream synthetic route of [ 1010814-94-4 ]

[ 1010814-94-4 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 5292-43-3 ]
  • [ 1010814-94-4 ]
YieldReaction ConditionsOperation in experiment
50.6% To a solution of diisopropylamine (13.5 ml, 96 mmol) in THF (300 ml) at -78C was added dropwise n-BuLi (2.5M in Hex, 32 ml). The mixture was warmed to -100C and re-cooled to -78C. A solution of 4-oxo-piperidine-l-carboxylic acid tert-butyl ester (10 g, 50 mmol) in THF (50 ml) was then added dropwise and the mixture stirred at -78C for another 15 min. A solution of tert-butyl bromoacetate (12.6 ml, 85 mmol) in THF (30 ml) and HMPT (5 ml) was then added dropwise and the mixture stirred at -78C for 4 h and then gradually warmed to rt. The mixture was taken up in sat. aq. NH4Cl and extracted with EA. The yield after work up and chromatography (eluent Hex/EA 4:1) was 7.6 g (50.6%; yellowish oil).1H NMR (CDCl3) delta: 4.40-4.20 (m, 2H); 3.25-3.15 (m, IH); 3.00-2.80 (m, 2H); 2.70-2.40 (m, 3H); 2.30-2.10 (m, IH); 1.51 (s, 9H), 1.46 (s, 9H).
  • 2
  • [ 1010814-94-4 ]
  • [ 1010814-95-5 ]
YieldReaction ConditionsOperation in experiment
60% Methyltriphenylphosphonium bromide (8.5 g, 23.9 mmol) was suspended in THF (23 ml) and treated with KOtBu (2.7 g, 23.9 mmol). The resulting yellow suspension was stirred at rt for 1 h. A solution of the intermediate 7.i (3.0 g, 9.6 mmol) in THF was added dropwise and the mixture was stirred at rt for 2 h, taken up in water and diluted with ether. The yield after work up and chromatography (Hex:EA 9:1) was 1.8 g (60%; colourless oil). 1H NMR (CDCl3) delta: 4.80 (s, IH); 4.75 (s, IH); 4.60-4.20 (m, 4H); 2.80-2.60 (m, IH); 2.50-2.25 (m, 3H); 2.25-2.10 (m, IH); 1.48 (s, 9H); 1.46 (s, 9H).
  • 3
  • [ 5292-43-3 ]
  • [ 79099-07-3 ]
  • [ 1010814-94-4 ]
YieldReaction ConditionsOperation in experiment
To a solution of diisopropylamine (7.41 g, 73.2 mmol) in dry tetrahydrofuran (150 mL) was added n-BuLi (2.5 M, 16 mL) dropwise at -70 C under nitrogen. The resultant mixture was warmed to -10 C and stirred for 30 min. The mixture was cooled to -70 C, and a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.00 g, 25.1 mmol) in dry tetrahydrofuran (20.0 mL) was added dropwise and stirred for 30 min. Then, a solution of tert-butyl 2-bromoacetate (4.89 g, 25.1 mmol) in tetrahydrofuran (20.0 mL) was added dropwise, followed by hexamethylphosphoramide (HMPA) (1.80 g, 11.0 mmol). On completion, to the mixture was added water (10 mL), and the solution was extracted with ethyl acetate (3 x 50 mL). The combined ethyl acetate phase was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether:ethyl acetate = 0:1 to 100:1) to give the title compound. 1H NMR (300 MHz, CDCl3) delta = 4.22 - 4.03 (m, 1H), 3.65 (t, J = 6.0 Hz, 2H), 2.83 (s, 1H), 2.57 - 2.33 (m, 4H), 2.32 - 2.06 (m, 1H), 1.43 (s, 9H), 1.38 (s, 9H).
  • 4
  • [ 1010814-94-4 ]
  • C26H35Cl2N3O5 [ No CAS ]
  • 5
  • [ 1010814-94-4 ]
  • (±)-tert-butyl 4-amino-3-(2-(tert-butoxy)-2-oxoethyl)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonium acetate; sodium cyanoborohydride; In tetrahydrofuran; at 20℃; for 16h;Molecular sieve; To a mixture of (±)-tert-butyl 3-(2-tert-butoxy-2-oxo-ethyl)-4-oxo-piperidine-1- carboxylate (2.00 g, 6.38 mmol) in tetrahydrofuran (20.0 mL) was added ammonium acetate (1.48 g, 19.1 mmol), followed by 4A MS (500 mg), and sodium cyanotrihydroborate (1.20 g, 19.1 mmol) in one portion at 20 C. The mixture was stirred at 20 C for 16 hrs. On completion, to the mixture was added water (30 mL) and the solution was extracted with dichloromethane (3 x 30 mL). The combined dichloromethane phase was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 10:1 to dichloromethane:methanol = 20:1) to give the title compound (crude).1H NMR (400 MHz, DMSO-d6) delta = 3.90 - 3.72 (m, 2H), 3.41 - 3.31 (m, 1H), 3.08 - 2.74 (m, 3H), 2.37 - 2.24 (m, 1H), 1.87 - 1.84 (m, 1H), 1.63 - 1.39 (m, 19H).
  • 6
  • [ 1010814-94-4 ]
  • [ 1010814-96-6 ]
 

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Technical Information

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