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Chemical Structure| 118753-66-5 Chemical Structure| 118753-66-5
Chemical Structure| 118753-66-5

*Storage: Keep in dark place,Inert atmosphere,2-8°C.

tert-Butyl 4-aminopiperazine-1-carboxylate

CAS No.: 118753-66-5

4.5 *For Research Use Only !

Cat. No.: A153848 Purity: 95%

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Product Details of [ 118753-66-5 ]

CAS No. :118753-66-5
Formula : C9H19N3O2
M.W : 201.27
SMILES Code : O=C(N1CCN(N)CC1)OC(C)(C)C
MDL No. :MFCD08274502
InChI Key :QMZFIRHRGPLKEV-UHFFFAOYSA-N
Pubchem ID :22029174

Safety of [ 118753-66-5 ]

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

Calculated chemistry of [ 118753-66-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.89
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 61.3
TPSA ?

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

58.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.15
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

0.18
Log Po/w (WLOGP)?

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

-0.35
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.

0.54
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

-0.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.35

Water Solubility

Log S (ESOL):?

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

-1.0
Solubility 20.0 mg/ml ; 0.0993 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.

-0.97
Solubility 21.4 mg/ml ; 0.106 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

-0.21
Solubility 125.0 mg/ml ; 0.619 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

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.

-7.4 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<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)

2.57

Application In Synthesis [ 118753-66-5 ]

* 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 [ 118753-66-5 ]
  • Downstream synthetic route of [ 118753-66-5 ]

[ 118753-66-5 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 877177-42-9 ]
  • [ 118753-66-5 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: With acetic acid; zinc In methanol at 0 - 20℃; for 2 h;
Stage #2: With sodium hydrogencarbonate In methanol; water
To a solution of the compound obtained in the above step (1) (730 mg) in methanol (10 mL) was added zinc powder (1.1 g) at room temperature and thereto was added dropwise acetic acid (10 mL) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered and to the filtrate was added an aqueous sodium hydrogencarbonate solution to basify. After stirring, the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to obtain l-amino-4-tert- butoxycarbonylpiperazine (730 mg, yield: 100 percent) as a pale yellow oil.
58% With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 25℃; for 12 h; To a solution of 1 ,1 -dimethylethyl 4-nitroso-1 -piperazinecarboxylate (500 mg, 2.33 mmol) in THF (23 mL) at O0C was added dropwise a solution of LAH (5.8 mL, 5.8 mmol, 1 M in THF). The reaction mixture warmed to 25°C over 12h and was subsequently quenched by dropwise addition of a saturated solution of potassium sodium tartrate. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4) and concentrated at 250C yielding a yellow oil that was used without further purification (270 mg, 58percent): LCMS (ES) m/e 202 (M+H)+.
References: [1] Patent: WO2007/46550, 2007, A1, . Location in patent: Page/Page column 120.
[2] Patent: WO2006/20561, 2006, A2, . Location in patent: Page/Page column 61.
[3] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 247 - 258.
[4] Patent: US10213433, 2019, B2, . Location in patent: Paragraph 0680.
  • 2
  • [ 883554-88-9 ]
  • [ 118753-66-5 ]
References: [1] Patent: US2009/275594, 2009, A1, . Location in patent: Page/Page column 19.
  • 3
  • [ 24424-99-5 ]
  • [ 30651-60-6 ]
  • [ 118753-66-5 ]
References: [1] Patent: US2003/199689, 2003, A1, . Location in patent: Page/Page column 76.
  • 4
  • [ 118753-70-1 ]
  • [ 118753-66-5 ]
References: [1] Patent: US4839358, 1989, A, .
  • 5
  • [ 57260-71-6 ]
  • [ 118753-66-5 ]
References: [1] Patent: WO2015/22663, 2015, A1, .
[2] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 247 - 258.
[3] Patent: US10213433, 2019, B2, .
 

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