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Structure of 129799-14-0

Chemical Structure| 129799-14-0

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Product Details of [ 129799-14-0 ]

CAS No. :129799-14-0
Formula : C19H26N2O6
M.W : 378.42
SMILES Code : O=C(N1C(C(OC)=O)CN(C(OCC2=CC=CC=C2)=O)CC1)OC(C)(C)C
MDL No. :MFCD09038774
InChI Key :JHEYLNAAOWKKBQ-UHFFFAOYSA-N
Pubchem ID :22498401

Safety of [ 129799-14-0 ]

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

Computational Chemistry of [ 129799-14-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 27
Num. arom. heavy atoms 6
Fraction Csp3 0.53
Num. rotatable bonds 9
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 105.27
TPSA ?

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

85.38 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.83
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

2.24
Log Po/w (WLOGP)?

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

1.5
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.

1.53
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

1.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.05

Water Solubility

Log S (ESOL):?

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

-3.17
Solubility 0.257 mg/ml ; 0.000679 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.

-3.67
Solubility 0.0812 mg/ml ; 0.000214 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

-2.96
Solubility 0.417 mg/ml ; 0.0011 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

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

Yes
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

Yes
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

Yes
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.

-7.02 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<2.0
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)

3.65

Application In Synthesis of [ 129799-14-0 ]

* 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 [ 129799-14-0 ]

[ 129799-14-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 129799-14-0 ]
  • [ 149057-19-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In methanol; (A) 1-tert-Butoxycarbonyl-4-Benzyloxycarbonylpiperazine-2-Carboxylic Acid 1 N Sodium hydroxide solution (0.92 mL) was added to a solution of methyl 1-tert-butoxycarbonyl-4-benzyloxycarbonylpiperazinyl-2-carboxylate (346 mg) in methanol (5 mL). After stirring at room temperature for 3 hr, the solvents were removed in vacuo. The residue was diluted with water and washed with diethyl ether. The aqueous layer was acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo to afford the title compound (237 mg) as a pale yellow oil. The compound appears as a mixture of rotamers: 1H NMR (400 MHz, CDCl3) delta 1.44 and 1.47 (each s, total 9H), 2.82-3.05 (m, 1H), 3.05-3.42 (m, 2H), 3.72-3.97 (m, 1H), 3.97-4.19 (m, 1H), 4.554.90 (m, 2H), 5.00-5.28 (m, 2H), and 7.20-7.42 (m, 5H).
  • 2
  • [ 149057-19-2 ]
  • [ 74-88-4 ]
  • [ 129799-14-0 ]
YieldReaction ConditionsOperation in experiment
96.4% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; Step 4 Synthesis of <strong>[149057-19-2]piperazine-1,2,4-tricarboxylic acid 4-benzyl ester 1-tert-butyl ester</strong> 2-methyl ester K2CO3 (910 mg, 6.6 mmol) was added to a stirred solution of <strong>[149057-19-2]piperazine-1,2,4-tricarboxylic acid 4-benzyl ester 1-tert-butyl ester</strong> (1.2 g, 3.3 mmol) in DMF (10 mL) at ambient temperature. To the above mixture was added at 0 C., CH3I (1.4 g, 9.9 mmol) and stirred 20 C. for 2 hr. The reaction mixture was diluted with cold water, extracted with ethyl acetate and dried over sodium sulphate, concentrated under reduced pressure to afford 1.2 g(96.4%) of <strong>[149057-19-2]piperazine-1,2,4-tricarboxylic acid 4-benzyl ester 1-tert-butyl ester</strong> 2-methyl ester.
55% With caesium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 4h; Example 52 - Preparation of Intermediate 17 The synthesis of Intermediate 17 followed the procedure of General Procedure 13 following: Intermediate 16 Intermediate 17 To a cooled solution (0C) of 4-(benzyloxycarbonyl)-1-(tert- butoxycarbonyl)piperazine-2-carboxylic acid (Intermediate 16, 20 g, 54.9 mmol) in dry DMF (200 mL) was added cesium carbonate (Cs2CO3, 35.8 g, 109.9 mmol) followed by methyl iodide (10.26 mL, 164.83 mmol). The reaction mixture was stirred at room temperature for 4 hours. After cooling to 0 C the mixture was quenched with ice-cold water (90 mL), and extracted with EtOAc (2 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (100-200 mesh), eluting with 20% EtOAc/n-hexane, to afford 4- benzyl 1-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate (Intermediate 17, 25 g, yield-55%) as an off-white solid. TLC: 30% ethyl acetate in hexane. Rf: 0.5.
 

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Technical Information

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